FTL encodes the 175-residue human ferritin light chain. Its principal role is within the cytosolic ferritin shell, where L-chain composition supports mineral formation and controls iron availability. Recombinant human L-chain homopolymers incorporate iron, and experiments with mixed H/L shells distinguish shell effects from H-chain catalytic oxidation (PMID:19923220; PMID:20159981). Human L-chain-deficient fibroblasts can sequester more iron in H homopolymers while their labile iron pool falls; wild-type L-chain transduction partly restores availability (PMID:23940258). Thus FTL loss need not simply reduce total iron storage.
Identical-subunit binding is a characteristic shell-assembly property, supported by recombinant L-chain structures and positive wild-type self-association (PMID:16790936; PMID:25910212). Interaction screens also recover FTH1 and contextual partners. Human proteins in yeast, tagged proteins in mammalian cells, co-complex AP-MS and purified assemblies answer different questions. A screen-wide validation rate does not certify an individual FTL pair. The exact 2015 Table S3A distinguishes positive wild-type FTL–FTH1/self interactions from A96T/H133P loss; its GPCA table contains no FTL pair. The 2014 and 2019 original variant calls differ and remain attributed to their own assays (PMID:25502805; PMID:31515488).
Ferritin containing FTL is cargo during receptor-dependent turnover. NCOA4-associated recovery, lysosomal delivery and cargo-composition knockout/rescue do not alone show that FTL performs an autophagy step (PMID:24695223; PMID:25327288). The 2024 original actually tests human wild-type FTL and engineered L2H; it distinguishes productive FTH1 receptor contact from the properties of wild-type L chain (PMID:38714719). A separately encountered 2019 indexed original excerpt reports FTL knockout/rescue effects on degradation and colocalization; this necessity evidence is retained as a caveat, without claiming that its full Methods were read or that cargo necessity resolves participation (Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions, PMC6597882).
Cytosol and ferritin-complex membership describe the principal storage setting. Granule/extracellular and autophagic compartments are contextual locations. Human urinary exosome proteomics directly identifies FTL with the original urine scope (PMID:19056867); another urine-fraction study has accessible main text but an unrecovered exact FTL supplementary row (PMID:23533145). The membrane-proteomics claim remains unresolved without its exact target row (PMID:19946888). The inspected erythropoiesis study perturbs mouse NCOA4 and iron supply, leaving FTL-specific differentiation unresolved (PMID:26776506).
The phylogeny retains all three positive root IBDs on the exact human target path. Iron-binding capacity is not equivalent to H-like ferroxidase activity, and legitimate target self-evidence is not circular. Official is_a links justify the iron-binding granularity decisions; the cytosol part_of cytoplasm link justifies the three cytoplasm decisions. No new function is inferred from uninspected family nodes.
The proposed review retains 20 core assertions and 44 contextual assertions, marks six broad assertions too general and one autophagy participation assertion over-annotated, and leaves two source-specific assertions unresolved. All original contexts are preserved. That initial assessment introduced no new annotation, quotation or natural alternative product. The scientific assessment was prepared before native acquisition. Its source-specific access limits and original contexts remain documented in the source guide and evidence archive.
The repository tools produced the native UniProt record, GOA export and untouched 73-row PENDING seed. Every original context and all 16 TSV columns were joined to their actual stored rows; forecast positions remain separately identified. All 55 planned normal sources are present: 37 existing files were reused unchanged and 18 were acquired natively, including eight bibliography-only papers and two Reactome entries fetched explicitly. Existing PANTHER entries, metadata and PAINT files were preserved; all three incoming IBD assertions match the retained target-path evidence.
The original urinary-exosome scope is restored in this transfer as part_of urine, with the literal source expression retained in the evidence archive. The three suggested questions retain their complete rationale within the schema-supported question text. The accepted 73 review decisions, two core functions and 57 reference assessments are unchanged. The accepted decisions and synthesis have been applied to the genuine 73-row seed, preserving its machine fields and restoring the original urine scope. Actual validation, computed status and history outcomes follow in the outcome appendix. Known provider credential holds remain in effect; no provider output or retry is claimed.
Default schema, ontology, reference and best-practice validation passed, together with strict GOA reconciliation of all 73 annotations. The 34 advisories concern intentionally retained generic protein-binding contexts whose source-specific assays do not establish a more informative shared molecular function. The native status audit confirms DRAFT. Both unresolved source-specific contexts remain UNDECIDED; no scientific decision was changed to suppress warnings. All 55 normal sources remain byte-identical to the acquisition record. The genuine CREATE history and rendered preview were checked, including the links to the source guide and evidence archive.
The 73 annotation actions remain unchanged. The structured synthesis now separately represents inherited ferrous-ion binding, ferric-iron storage and the L-chain contribution to shell structural integrity. The two experimental broad iron-binding rows retain their original evidence codes and remain TOO_GENERAL: iron incorporation and retention are not equated with an isolated valence-specific binding assay. Pore-dependent iron movement is retained with explicit primary support because the GO transport definition includes movement within a cell through a pore.
Partner-specific reasons distinguish yeast two-hybrid pairs from co-complex AP-MS recovery. There is no generic self-binding row to reassign, and FTH1 association alone does not establish a two-subunit heterodimer. The evidence archive contains original interaction-record excerpts, exact source locators and provenance for five newly checked literal snippets. The dated acquisition and validation entries above record the initial publication state; revised validation outcomes are recorded below.
Default schema, ontology, reference and best-practice validation and strict GOA reconciliation of all 73 annotations pass. The native status audit confirms DRAFT with 35 advisories: 34 retained generic protein-binding contexts and structural molecule activity represented in the shell core without a separate GOA annotation. All 73 annotation actions remain unchanged, including both source-specific UNDECIDED judgments. Exactly five checked quotation associations are present. No annotation was added to suppress an advisory. All 55 source files and the original CREATE history remain unchanged. The new EDIT history is linked to PR #5818. History validation and the private rendered review were checked, including all 73 annotation rows, three core functions and 58 references.