Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth (PubMed:11311121, PubMed:12588975, PubMed:16511445, PubMed:16611631, PubMed:17349958, PubMed:18599021, PubMed:22307329, PubMed:9748265). Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1 (PubMed:11311121, PubMed:12588975, PubMed:16511445, PubMed:16611631, PubMed:17349958, PubMed:18599021, PubMed:22307329, PubMed:38968120). Can phosphorylate histone H1, histone H3 and histone H2B (in vitro) (PubMed:9748265). Can phosphorylate CARHSP1 (in vitro) (PubMed:15910284). Functions in part via its role in ubiquitin-dependent proteasomal protein degradation (PubMed:9748265). Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage (PubMed:17349958, PubMed:18599021). Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity (PubMed:16511445). May play a general role in the priming of GSK3 substrates (PubMed:11311121, PubMed:16611631). Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B (PubMed:11311121). Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B (PubMed:16611631). Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis (PubMed:14593110). Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1 (PubMed:19287380). Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex (PubMed:23362280). Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity (PubMed:22878263). Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation (PubMed:22307329). Acts as a positive regulator of smoothened signaling by mediating phosphorylation of GLI2 and GLI3 in response to smoothened activation, promoting their dissociation from SUFU inhibitor and translocation to the nucleus (PubMed:38968120). Can also acts as a negative regulator of smoothened by catalyzing phosphorylation of GLI2 and GLI3 and promote their proteasomal degradation (PubMed:18455992). Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2 (By similarity). {ECO:0000250|UniProtKB:Q5U4C9, ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:38968120, ECO:0000269|PubMed:9748265}. This is the function of ENSG00000127334 (DYRK2, dual specificity tyrosine phosphorylation regulated kinase 2).