Applied the annotation-reviewer and core-function-synthesizer criteria to the genuine human FLNC seed and the independently reviewed primary-source consultations. All 32 original contexts map one-to-one to 32 stored review rows. Final planned decisions are 11 ACCEPT, 8 KEEP_AS_NON_CORE, 9 MODIFY and 4 TOO_GENERAL. There are no NEW annotations, no publication quotations, two unchanged natural products and one structural core.
The core combines actin-filament binding, sarcomere organization and documented muscle structural contacts. It does not transfer myotilin's proposed alpha-actinin bridge, Xin's other ligand interfaces or ankyrin's membrane behavior to a separate FLNC activity. PMID:11038172(https://pubmed.ncbi.nlm.nih.gov/11038172/), PMID:16076904(https://pubmed.ncbi.nlm.nih.gov/16076904/), PMID:34405687(https://pubmed.ncbi.nlm.nih.gov/34405687/)
Nine generic-binding contexts receive informative evidence-backed subtypes. The two remaining generic associations are supported but lack an established narrower FLNC activity and remain non-core under the campaign instruction. Exact pair, fragment, species and natural-product limits are retained. Product 2's 1734–1766 deletion overlaps one tested SH3-binding peptide but not the separately positive 260–273 peptide; no complete binding loss is inferred.
The original raw4 occurs_in GO:0014704 extension and all original partner/context fields are retained in the context guide and typed projection proof. The source's human/chicken nebulette contexts, rat O70511-7 Ank3 context and mouse/rat donor transfers are not silently relabeled. The experimental PMID:12393796 cytoplasm assertion is not rejected because the selected primary sections foreground other filamins; its correct broad compartment is covered by independent target evidence, and exact source-specific FLNC support remains explicitly unverified.
Eleven existing main sources were hydrated and hash-checked before genuine fetch. Six absent publications were fetched normally, including the additional mouse-donor PMID:16914736. All 17 normal sources are present, with existing bytes preserved. PTHR38537 sources are reused unchanged from accepted FLNA work; its genuine single plant-branch PAINT record is not on the human target path, and FLNC has no incoming IBA. No bulk family archive was downloaded. Existing provider credential/quota failures were not retried; the evidence synthesis honestly records manual primary research rather than a fabricated provider report.
The evidence synthesis and source guide preserve actual reading limits, original URLs, ontology paths, source identities and product boundaries. Validation and independent canonical peer review follow the scientific authoring; their results will be appended here.
All seven scoped checks passed: schema/best practices/term and reference checks, strict GOA matching, history schema, deterministic status, private rendering and whitespace checks. The status remains DRAFT. Exactly two advisories concern the supported FBXL22/RTF2 generic-binding rows retained as non-core under the campaign instruction; these are not unresolved interaction claims. The PMID markdown helper found no pathway files and did not validate these notes. The shared runtime emitted a dependency deprecation warning; no environment was created. Independent canonical peer review read all 32 decisions and supporting documents, replayed exact seed/context/product preservation and found no scientific issue. Two duplicated citation prefixes were then corrected without changing any assertion.
The two original annotation extensions are now rehydrated in the structured YAML: raw4/stored4 occurs_in GO:0014704 and raw25/stored17 part_of CL:0000057. These reproduce the original QuickGO contexts rather than adding biological assertions. All other source fields and original raw objects remain unchanged. The cytoskeleton location is refined to actin cytoskeleton using the actual tagged human FLNC localization experiment in rat cardiomyocytes, with its construct and host limits preserved. Sarcomere organization already entails actin cytoskeleton organization through actomyosin structure organization; the single core is unchanged. Final decisions are 10 ACCEPT, 8 KEEP_AS_NON_CORE, 10 MODIFY and 4 TOO_GENERAL across the same 32 contexts. The two natural products and single structural core are unchanged.
The actual localization observation is in PMID:25351925, Results, Functional analysis of FLNC mutations (author-copy text lines 301–306), with the human construct and rat host separately recorded. The process coverage follows the official is_a path GO:0045214 → GO:0031032 → GO:0030036. PMID:25351925(https://pubmed.ncbi.nlm.nih.gov/25351925/), actin cytoskeleton, sarcomere organization
The PMID:34405687 Results distinguish structural defects in FLNC-null human cardiomyocytes from protein accumulation, lysosome changes and altered autophagic flux in the tested heterozygous variants. Its Discussion places ubiquitinated FLNC among proteins disposed of by BAG3 and p62. This turnover context does not establish FLNC as a chaperone or as an executor of selective autophagy, and no NEW process is proposed. The current sources do not establish an HSPB8-specific assay in these experiments. Likewise, cellular actin-bundle disruption and the paper's background crosslinking description are not a purified FLNC crosslinking measurement. These limits support retaining the current binding core while asking what direct biochemical evidence is available. PMID:34405687(https://pubmed.ncbi.nlm.nih.gov/34405687/)
Supported FBXL22/RTF2 generic associations remain non-core, and no new publication quotations are added, under the published campaign instructions. Reference-only support, exact source locators and access boundaries remain explicit. No normal cache or committed history is rewritten.