MFSD6L

MFSD6L is an acrosome membrane protein required for acrosome biogenesis and sperm head shaping during spermatogenesis (PMID:38909778). It localizes to the sperm acrosome membrane and physically interacts with the inner acrosomal membrane protein SPACA1, supporting acrosome architecture and anchoring (PMID:38909778). Loss of MFSD6L through bi-allelic loss-of-function variants in humans or gene knockout in mice causes oligoasthenoteratozoospermia, with reduced sperm concentration, impaired motility, and deformed acrosomes, linking MFSD6L deficiency to male subfertility (PMID:38909778). Beyond this single focused study, no further mechanistic detail — including any transporter activity or molecular role outside the acrosome — has been characterized in the available corpus.

1. 2024 High

   Established that MFSD6L is an acrosome membrane protein whose loss disrupts acrosome formation and sperm head morphology, defining its role in spermatogenesis and male fertility.

   Evidence Human bi-allelic loss-of-function variant analysis, Mfsd6l knockout mouse phenotyping, subcellular localization to the acrosome membrane, and co-immunoprecipitation with SPACA1

   PMID:38909778

   Open questions at the time

   • Molecular function of MFSD6L (e.g. any transport activity implied by its MFS-type name) is not defined
   • The mechanism by which MFSD6L–SPACA1 interaction shapes the acrosome is not resolved structurally
   • No reciprocal validation or mapped interaction interface for the SPACA1 binding is reported

• Whether MFSD6L has an intrinsic biochemical/transport activity and how it is recruited to and organizes the acrosomal membrane remains unknown.
• No substrate or transport assay has been reported
• No structural model of MFSD6L or its complex with SPACA1
• Role outside sperm, if any, is uncharacterized