DRC5 (dynein regulatory complex subunit 5, also known as TCTE1) is a conserved component of the nexin-dynein regulatory complex (N-DRC) that regulates ciliary and flagellar motility 1. As an N-DRC component localized between doublet microtubules, DRC5 coordinates dynein arm activity and maintains axonemal structural integrity 2. The protein contains a leucine-rich repeat domain and is highly expressed in testis, particularly in developing spermatids 1. DRC5 functions to regulate ATP metabolism in flagella; Tcte1-knockout spermatozoa show structurally normal axonemes but demonstrate aberrant motility and significantly reduced ATP levels (2.4-fold lower), indicating DRC5's role in energy-dependent dynein function 13. Mutations in human DRC5/TCTE1 cause asthenospermia characterized by normal sperm morphology but severely reduced motility 4. Clinical and mouse studies reveal that DRC5 variants impair N-DRC protein assembly and localization to the flagellum, disrupting sperm tail beating patterns 3. Homozygous Tcte1-knockout males are completely infertile, while heterozygotes show haploinsufficiency with oligozoospermia 3. Notably, DRC5 mutations account for approximately 6% of asthenozoospermia cases in infertile males, establishing DRC5 as clinically significant for male fertility 3. Intracytoplasmic sperm injection successfully overcomes DRC5-related infertility in humans 4.