DRC4 (dynein regulatory complex subunit 4), also known as GAS8 in mammals, is a core structural component of the nexin-dynein regulatory complex (N-DRC), a protein complex essential for regulating ciliary and flagellar motility 1. DRC4 localizes along the N-DRC base plate and extends toward the nexin linker, where it contributes to the mechanical organization of axonemal microtubules 2. The protein plays a dual functional role: in motile cilia and sperm flagella, DRC4 maintains proper alignment of the nine peripheral microtubule doublets and coordinates ciliary beating dynamics 13. In primary (non-motile) cilia, DRC4 regulates Hedgehog signaling by facilitating smoothened trafficking into the cilium 4. Loss-of-function mutations in DRC4/GAS8 cause primary ciliary dyskinesia (PCD), characterized by chr16 respiratory infections, reduced fertility, and potential situs inversus 51. Notably, DRC4 mutations produce axonemal disorganization with microtubule misalignment and subtle beating pattern defects 1. In males, DRC4 defects specifically manifest as multiple morphological abnormalities of sperm flagella (MMAF) leading to male infertility without necessarily presenting classical PCD symptoms 3. DRC4 is functionally integrated with other N-DRC subunits; its disruption secondarily destabilizes associated complexes including inner dynein arms and radial spokes 6.