Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins (PubMed:31308046, PubMed:35545041, PubMed:37926288). Via its catalytic activity, regulates many processes, including cell proliferation, cell differentiation, inflammatory response and apoptosis. Regulates the inflammatory response by mediating mono- and dimethylation of 'Lys-4' of histone H3 (H3K4me1 and H3K4me2, respectively), leading to activate the transcription of pro- inflammatory cytokines IL6 and TNF (By similarity). Through the catalysis of TBK1 monomethylation, may regulate virus-induced interferon signaling. TBK1 monomethylation enhances its interaction with MAVS, STING and IRF3, hence promoting antiviral interferon signaling (PubMed:37926288). Also involved in the regulation of stem cell quiescence by catalyzing the trimethylation of 'Lys-20' of histone H4 (H4K20me3), thereby promoting heterochromatin formation (PubMed:31308046). In the brain, epigenetically controls quiescence of neural stem cells for sustaining a protected neural stem cell population and maintaining a stem cell reservoir for neurogenesis (By similarity). Involved in proliferation, migration, paracrine and myogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) (By similarity). Through the catalysis of XRCC5/Ku70 trimethylation, regulates BAX-mediated apoptosis. SETD4-catalyzed XRCC5 methylation results in XRCC5 translocation to the cytoplasm, where it interacts with BAX, sequestering it from the mitochondria, hence preventing BAX- mediated apoptosis (PubMed:35545041). {ECO:0000250|UniProtKB:P58467, ECO:0000269|PubMed:31308046, ECO:0000269|PubMed:35545041, ECO:0000269|PubMed:37926288}. This is the function of ENSG00000185917 (SETD4, SET domain containing 4).