EFCAB5 (EF-hand calcium binding domain 5) is a calcium-binding protein with emerging roles in neurological and reproductive biology. Primary function involves regulation of axonemal structures critical for sperm motility; Efcab5 knockout mice show reduced sperm motility and fertility, with EFCAB5 identified as a sperm-specialized movement regulator interacting with radial spoke protein CFAP91 1. In the brain, EFCAB5 is associated with epigenetic aging rates across multiple brain regions, with significant cis-expression quantitative trait loci identified at locus 17q11.2 (P=3.4×10⁻²⁰) 2. The gene demonstrates disease relevance across multiple conditions: it was prioritized in glymphatic system function studies and associated with neurodegenerative diseases, with lower glymphatic function representing a risk factor for ischemic stroke 3. EFCAB5 also shows prognostic significance in skin cutaneous melanoma, where its expression associates with poor prognosis 4, and was identified as a novel cancer gene in biliary tract cancers associated with primary sclerosing cholangitis 5. Additionally, rare truncating variations in EFCAB5 were identified in a family with autism spectrum disorder, suggesting potential involvement in neurodevelopmental conditions 6. These findings indicate EFCAB5 functions across reproductive, neurodegenerative, and oncologic contexts.