PIAS3 also designated ZMIZ5 is a member of the PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)] family of transcriptional modulators. PIAS3 plays a crucial role in regulating signal transduction pathways mediated by the IL-6-type family of cytokines, which are essential for gene activation, cell proliferation, and differentiation. Specifically, PIAS3 functions as a negative regulator of the transcription factor Stat3, which is activated in response to cytokine signaling. By binding to Stat3, PIAS3 inhibits DNA-binding activity, thereby preventing transcription of target genes crucial for various cellular processes, including inflammation and immune responses. This regulatory mechanism is vital for maintaining cellular homeostasis and preventing excessive activation of Stat3, which can lead to pathological conditions such as cancer and autoimmune diseases.