The function of PIAS4 (protein inhibitor of activated STAT 4, ENSG00000105229) is as follows. 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 (PubMed:12511558, PubMed:12631292, PubMed:12727872, PubMed:15831457, PubMed:15976810, PubMed:22508508, PubMed:32832608). Mediates sumoylation of ALKBH5, AXIN1, CEBPA, KLF8, GATA2, PARK7, HERC2, MYB, TCF4 and RNF168 (PubMed:12223491, PubMed:12511558, PubMed:12631292, PubMed:12727872, PubMed:12750312, PubMed:15831457, PubMed:15976810, PubMed:16617055, PubMed:22508508, PubMed:34048572). Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway (PubMed:11388671). Involved in gene silencing (PubMed:11248056). In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations (PubMed:12727872, PubMed:15831457). Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (PubMed:21965678). Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (By similarity). Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage, facilitating repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:32832608). Mediates sumoylation of PARP1 in response to PARP1 trapping to chromatin (PubMed:35013556). Mediates sumoylation of KLF8, repressing KLF8 transcriptional activity and cell cycle progression into G(1) phase (PubMed:16617055). Sumoylates ALKBH5 downstream of MAPK8/JNK1 and MAPK9/JNK2 in response to reactive oxygen species (ROS), inhibiting ALKBH5 RNA demethylase activity (PubMed:34048572). {ECO:0000250|UniProtKB:Q9JM05, ECO:0000269|PubMed:11248056, ECO:0000269|PubMed:11388671, ECO:0000269|PubMed:12223491, ECO:0000269|PubMed:12511558, ECO:0000269|PubMed:12631292, ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:12750312, ECO:0000269|PubMed:15831457, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:16617055, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:22508508, ECO:0000269|PubMed:32832608, ECO:0000269|PubMed:34048572, ECO:0000269|PubMed:35013556}.