EFCAB5

EFCAB5 is a sperm-specialized axonemal component required for normal sperm motility and male fertility (PMID:40931011). It was identified as a CFAP91-proximal protein in mature spermatozoa, placing it within the radial spoke/axonemal framework, and loss of EFCAB5 in mice reduces sperm motility and fertility (PMID:40931011). Beyond this proximity relationship and knockout phenotype (PMID:40931011), no further mechanistic detail—including direct binding partners, molecular activity, or the structural basis of its role in flagellar movement—has been characterized in the available corpus.

1. 2025 Medium

   Whether EFCAB5 has a defined role in sperm function was unknown; proximity labeling and knockout established it as an axonemal motility regulator near the radial spoke protein CFAP91.

   Evidence BioID2 proximity labeling with CFAP91 in transgenic mice plus Efcab5 knockout mouse with sperm motility and fertility readouts

   PMID:40931011

   Open questions at the time

   • Direct physical interaction with CFAP91 not demonstrated (proximity labeling only, no reciprocal Co-IP or reconstitution)
   • Molecular activity of EFCAB5 and its structural placement within the radial spoke unresolved
   • Mechanism by which loss reduces motility (specific flagellar defect) not defined

• The biochemical function of EFCAB5 and its direct molecular partners within the axoneme remain undefined.
• No direct binding partner confirmed
• No structural or biochemical activity characterized
• Human fertility relevance not established