WDR64

WDR64 is a testis-specific WD40-repeat protein with two β-propeller domains that participates in spermiogenesis through a physical association with the outer dense fiber protein ODF1 (PMID:39386799). The WDR64/ODF1 complex localizes to the manchette during the nuclear-shaping phase of spermatid elongation and subsequently to the midpiece of mature spermatozoan flagella, placing WDR64 at structures that govern manchette-directed intracellular transport and flagellum assembly (PMID:39386799). Beyond this interaction and its dynamic localization across spermatid development (PMID:39386799), no loss-of-function phenotype, structural model, or biochemical activity has been characterized in the available corpus.

1. 2024 Medium

   Whether the testis-specific protein WDR64 has a defined partner and cellular location during sperm development was unknown; identifying its interactor and localization established a candidate role in manchette and flagellum assembly.

   Evidence IP–MS identification of ODF1 as an interactor plus stage-resolved immunofluorescence, RT-PCR, and Western blot in testis/spermatids

   PMID:39386799

   Open questions at the time

   • No loss-of-function or knockout phenotype to establish functional requirement
   • Interaction shown by Co-IP/MS without reciprocal validation or in vitro reconstitution
   • Molecular activity of the WD40 β-propellers and the functional consequence of the ODF1 association are undefined

• It remains unknown whether WDR64 is required for manchette-directed transport or flagellum assembly and what cargo or molecular function its β-propellers mediate.
• No in vivo gene disruption to test a role in fertility or sperm morphogenesis
• No mapping of the WDR64–ODF1 interaction interface or structural characterization