ZNF764 is a C2H2-type zinc finger protein that functions as a cofactor for steroid hormone receptors, particularly the glucocorticoid receptor (GR) 1. The protein directs GR transcriptional activity toward specific biologic pathways by modulating GR binding and transcriptional activity on glucocorticoid-responsive genes 1. Mechanistically, ZNF764 physically interacts with GR through its KRAB domain at the ligand-binding domain, with both the KRAB domain and zinc finger domain required for regulatory function 1. Genome-wide analysis reveals that ZNF764 and GR-binding sites show similar genomic distributions, overlapping in approximately 37% of sites, predominantly positioned 50-500 kb from transcription start sites 1. Clinically, ZNF764 haploinsufficiency resulting from 16p11.2 microdeletion causes partial resistance to glucocorticoids, androgens, and thyroid hormones 2. A patient with heterozygous 16p11.2 microdeletion encompassing ZNF764 exhibited multiple hormone resistance with developmental delay and autism spectrum disorder features 2. Experimental evidence demonstrates that ZNF764 knockdown significantly reduces glucocorticoid-, androgen-, and thyroid hormone-induced transcriptional activity, while overexpression enhances it 2. Exogenously supplemented ZNF764 restored glucocorticoid responsiveness in patient-derived lymphocytes, confirming its functional importance 2. The protein cooperates with transcriptional intermediary factor 1, a general nuclear hormone receptor coactivator 2.