ZNF341 (zinc finger protein 341) is a transcriptional activator that regulates STAT3 expression and plays a critical role in immune homeostasis 1. The protein functions as a transcription factor controlling STAT3 gene transcription, with ZNF341-deficient cells showing approximately 50% normal STAT3 levels in resting state and impaired STAT3 autoinduction 2. Biallelic complete loss-of-function variants in ZNF341 cause autosomal recessive hyper-IgE syndrome type 3 (HIES-3), characterized by eczema, recurrent bacterial and fungal infections, elevated serum IgE levels, and susceptibility to Staphylococcus aureus infections 23. The pathophysiological mechanism involves both decreased basal STAT3 expression and impaired STAT3 autoinduction rather than simple haploinsufficiency 2. Clinically, ZNF341 deficiency presents with a milder phenotype compared to dominant-negative STAT3 mutations but includes similar manifestations such as cold abscesses, pulmonary infections, and lower NK cell counts 2. Patients also demonstrate increased radiosensitivity and impaired DNA repair mechanisms, potentially contributing to malignancy risk 4. Recent genome-wide association studies have identified ZNF341 as a susceptibility locus for community-acquired pneumonia, consistent with its role in immune function 5. The gene shows founder mutations in isolated populations with high consanguinity rates 6.