ZNF35 is a sequence-specific DNA-binding transcription factor that regulates gene expression through multiple mechanisms. The protein contains 11 consecutive zinc finger motifs at its amino terminus and an acidic transactivation domain at its carboxyl terminus, enabling it to recognize the core DNA sequence 5'-C/GC/GAAG/TA-3' 1. ZNF35 functions as a transcriptional transactivator in cultured cells 2. The gene spans approximately 13 kb on chromosome 3-p22, with all 11 zinc finger domains encoded within the final 3' exon 2. ZNF35 plays a critical role in male germ cell differentiation and spermatogenesis. Its mouse ortholog, Zfp105, is highly expressed in pachytene spermatocytes and round spermatids 3, and male fertility is reduced in Zfp105-deficient mice, which show impaired spermatogenic cell differentiation 4. ZNF35 protein localizes primarily to the cytoplasm of male germ cells 4. Regarding disease relevance, ZNF35 maps to chromosome 3-p22, a region frequently deleted in small cell lung and renal carcinomas 2. The zinc finger protein modulates CD58 expression through binding to regulatory motifs; the polymorphism rs10924104 in a ZNF35-binding site within CD58's enhancer is a primary functional variant conferring susceptibility to autoimmune diseases including systemic lupus erythematosus, multiple sclerosis, and primary biliary cholangitis 5.