RIBC1

RIBC1 is a microtubule inner protein (MIP) that localizes to the inner lumen of the doublet microtubules in mouse sperm flagella, where it acts together with its paralog RIBC2 to support sperm motility (PMID:40265983). Knockout of RIBC1 alone reduces sperm velocity, while combined loss of both RIBC1 and RIBC2 produces a markedly greater motility defect and reduced litter size, with RIBC2's contribution depending on RIBC1 and without axonemal structural abnormalities detectable by TEM (PMID:40265983). Beyond this localization and genetic role in flagellar motility (PMID:40265983), no further mechanistic detail—including binding partners, the structural basis of its association with the microtubule lumen, or molecular activity—has been characterized in the available corpus.

1. 2025 High

   Whether RIBC1 has a defined location and function within the sperm flagellar axoneme was unknown; this work established it as a microtubule inner protein essential for normal sperm motility and fertility.

   Evidence CRISPR/Cas9 single and double knockout mice with sperm motility analysis, fertility assays, TEM, and cryo-EM/AI structural localization

   PMID:40265983

   Open questions at the time

   • The molecular activity of RIBC1 and how it binds the doublet microtubule lumen are not defined
   • Direct physical partners, including the nature of the RIBC1–RIBC2 interaction, are not established
   • How loss of RIBC1 reduces motility without detectable axonemal structural defects is unexplained

• The biochemical mechanism by which RIBC1 stabilizes or organizes the doublet microtubule lumen to support flagellar beating remains unresolved.
• No structural model of RIBC1 bound within the microtubule lumen
• No identified molecular activity or direct interaction interface with tubulin or RIBC2