E3 SUMO-protein ligase PIAS4 also known as protein inhibitor of activated STAT protein 4 (PIAS4) or protein inhibitor of activated STAT protein gamma (PIASg or PIASy) is an enzyme that in humans is encoded by the PIAS4 gene.

Function: Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Promotes PARK7 sumoylation. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations.