ACTRT3 (actin-related protein T3) is a cytoskeletal protein localized to the perinuclear theca of spermatids that functions in acrosome biogenesis and sperm development 1. ACTRT3 operates as part of a three-dimensional protein scaffold in the perinuclear theca, interacting with multiple proteins including ACTRT1, ACTRT2, ACTL7A, SPEM2, and ZPBP 1. The protein regulates actin cytoskeleton remodeling, as expression of ACTRT3 induces changes in cell shape and F-actin filament distribution 1. Mechanistically, ACTRT3 facilitates Golgi trafficking and autophagic flux necessary for acrosome formation; its loss impairs Golgi protein localization and reduces autophagy markers LC3B, CTSB, and mTOR 1. Actin-related proteins like ACTRT3 are evolutionarily conserved and involved in cytoskeletal organization across tissues 2. Beyond reproductive function, ACTRT3 has disease relevance to cancer susceptibility: genome-wide and transcriptome-wide association studies identified ACTRT3 at the 3q26 locus as associated with multiple primary cancer development, suggesting involvement in telomere maintenance pathways 34. Additionally, systems biology analysis identified ACTRT3 as a central gene in B cell activation networks, indicating roles in immune regulation 5.