DCAF17 (DDB1 and CUL4 associated factor 17) functions as a substrate receptor for the CUL4-DDB1 E3 ubiquitin-protein ligase complex, playing a critical role in protein degradation pathways 1. The protein is essential for gonadal development and fertility, with loss-of-function variants causing severe reproductive dysfunction in both males and females 2. Pathogenic mutations in DCAF17 cause Woodhouse-Sakati syndrome (WSS), a rare autosomal recessive multisystemic disorder characterized by hypogonadism, alopecia, diabetes mellitus, intellectual disability, and sensorineural hearing loss 34. The syndrome shows significant phenotypic heterogeneity, with ectodermal and endocrine manifestations being the most consistent features 3. Various types of mutations have been identified, including splice site variants, frameshift deletions, and nonsense mutations, all leading to loss of protein function 56. DCAF17 variants are also associated with primary ovarian insufficiency and have been implicated in neurodegeneration with brain iron accumulation (NBIA), suggesting broader roles in cellular metabolism and neurological function 78. The protein appears critical for mammalian reproductive development, with mouse models demonstrating male infertility and female subfertility when Dcaf17 function is disrupted 2.