FER1L5 is a multi-domain ferlin family protein involved in calcium-triggered membrane dynamics critical for male fertility and skeletal muscle development. 1 As a dysferlin homologue, FER1L5 contains multiple C2-binding domains and a C-terminal transmembrane anchor that facilitate calcium-dependent membrane fusion events. 2 In spermatogenesis, FER1L5 is highly expressed in spermatids and plays a central role in the acrosome reaction, the calcium-activated fusion of the acrosomal membrane with the plasma membrane during fertilization. 3 Its dysregulation is associated with non-obstructive azoospermia (NOA), a common cause of male infertility, where FER1L5 expression is significantly reduced. 34 In myoblasts, FER1L5 localizes to vesicular structures and is enriched at fusion sites during differentiation, where it mediates myoblast fusion and membrane repair through interactions with vesicle trafficking machinery. 5 FER1L5 requires functional EHD1-mediated receptor recycling for proper localization and function in muscle development. 6 Additionally, genome-wide association studies have linked FER1L5 variants to blood pressure regulation. 7 Dysregulated ferlin expression, including FER1L5, may contribute to cancer development through effects on calcium signaling and membrane dynamics. 2