| Category | Key points | Evidence type (review/primary/model organism/database) | Key citations |
|---|---|---|---|
| Identity/domains | Human FBXL22 is the UniProt Q6P050/FXL22_HUMAN protein, a member of the FBXL subfamily with an N-terminal F-box domain and C-terminal leucine-rich repeats (LRRs); reviews describe a small FBXL protein with predicted ~3 LRRs and the canonical F-box/LRR architecture expected for substrate-binding adaptors. | Review/family annotation | (pqac-00000002, pqac-00000003, pqac-00000005) |
| Complex | FBXL22 is inferred/assigned as a substrate-recruiting component of a Cullin-1/Skp1 SCF-type E3 ubiquitin ligase complex; FBXL family proteins use the F-box to bind Skp1 and recruit substrates through LRRs. | Review with primary/model-organism support | (pqac-00000003, pqac-00000012, pqac-00000013) |
| Substrates | Best-supported reported substrates are sarcomeric α-actinin-2 (ACTN2) and filamin-C (FLNC); FBXL22-containing CRLs polyubiquitylate these proteins and promote proteasome-mediated degradation in striated-muscle systems. | Review summarizing primary/model-organism studies | (pqac-00000012, pqac-00000013) |
| Localization | FBXL22 is enriched in heart/striated muscle and localizes to the sarcomeric Z-disk, consistent with its proposed role in turnover of Z-disk/cytoskeletal proteins. | Review/model-organism evidence | (pqac-00000001, pqac-00000012) |
| Regulation | In skeletal muscle atrophy models, Fbxl22 mRNA rises early after denervation (~15-fold at day 3) and returns toward baseline by day 7; reviews also note induction during myogenic differentiation and neurogenic atrophy. Zebrafish regeneration work links fbxl22 expression to AP-1–dependent chromatin accessibility; a 2024 preprint suggests FoxO regulation as a hypothesis under investigation. | Review; model-organism primary; preprint/hypothesis | (pqac-00000007, pqac-00000006, pqac-00000011) |
| Biological roles/phenotypes | Core function is selective sarcomere/cytoskeletal protein quality control. Zebrafish loss of fbxl22 causes ACTN2 accumulation and progressive reduction in cardiac contractility. In murine skeletal muscle, overexpression causes transient muscle-mass increase but also myopathic changes (cell infiltration, necrosis, degeneration, centralized nuclei) and altered dystrophin, desmin, vimentin, and ACTN2; isoform-specific effects have been reported. | Review summarizing primary/model-organism studies | (pqac-00000012, pqac-00000006) |
| Human genetic/disease association evidence | Direct human functional disease evidence is limited. Human left atrial transcriptomic/coexpression studies include FBXL22 among candidate AF-related genes/resources, and Open Targets lists low-to-moderate association evidence for atrial fibrillation, dementia/Alzheimer disease, neurodegenerative disease, and type 2 diabetes based on aggregated datasets; these are association-level, not mechanistic proof. | Human transcriptomic association/database | (pqac-00000008, pqac-00000000) |


*Table: This table summarizes the currently supported functional annotation for human FBXL22 (UniProt Q6P050), separating well-supported molecular features from more tentative human disease associations. It is useful for distinguishing direct mechanistic evidence from broader association data.*