PJA2 (praja ring finger ubiquitin ligase 2) is an E2-dependent E3 ubiquitin-protein ligase 12 with diverse regulatory functions across multiple biological processes. Molecularly, PJA2 recognizes target proteins through its RING-B-box domain and catalyzes their ubiquitination-dependent proteasomal degradation 3. In neurobiology, PJA2 mediates PKA regulatory subunit degradation, essential for long-term memory formation 2. During ciliogenesis, PKA-phosphorylated OFD1 is ubiquitinated by PJA2 within a TBC1D31/praja2/PKA complex at centrosomes, promoting cilium biogenesis 4. Conversely, UFMylation of IFT88 antagonizes PJA2-mediated ubiquitination, maintaining ciliary homeostasis 5. In immune regulation, PJA2 positively regulates TLR2 signaling via MFHAS1 ubiquitination 6 but negatively restrains type I interferon signaling by promoting non-degradative ubiquitination of TYK2 and JAK1 7. PJA2 also controls antiviral responses by degrading PWWP3A, enabling viral defense 8. Clinically, PJA2 suppresses colorectal cancer by degrading HDAC2, activating IFIT genes 3. In gastric cancer, low PJA2 allows CHR5 accumulation, promoting tumor progression via TGFβ signaling; PJA2 restoration or mAChR inhibitors represent therapeutic strategies 9. PJA2 also regulates Alzheimer's disease markers in hippocampal neurons 10.