| Functional category | CDK5 substrate | Phosphorylation site(s) | Functional outcome | Citation |
|---|---|---|---|---|
| Synaptic function | Munc18 | S158 | Promotes dissociation from Syntaxin 1A, facilitating synaptic vesicle fusion and neurotransmitter release | (pqac-00000005, pqac-00000008) |
| Synaptic function | PSD-95 | T19, S25, S35 | Regulates synaptic plasticity; phosphorylation reduces clustering with ion channels and promotes degradation | (pqac-00000005, pqac-00000008) |
| Synaptic function | NR2A | S1232 | Enhances NMDA receptor function and contributes to synaptic plasticity | (pqac-00000005, pqac-00000008) |
| Synaptic function | Dynamin I | S774, S778 | Increases clathrin-mediated endocytosis | (pqac-00000005, pqac-00000008) |
| Synaptic function | Amphiphysin I | S272, S276, S285 | Increases clathrin-mediated endocytosis | (pqac-00000005, pqac-00000008) |
| Synaptic function | TrkB | S478 | Regulates activity-dependent structural plasticity and spatial memory | (pqac-00000008) |
| Synaptic function | SPAR | S1328 | Primes SPAR for degradation, promoting synaptic weakening/homeostatic scaling | (pqac-00000008) |
| Synaptic function | Liprinα1 | T701 | Enhances excitatory synaptic function by regulating PSD-95-associated localization | (pqac-00000008) |
| Synaptic function | CaV2.2 | S2013 | Regulates Ca2+ influx at presynaptic terminals | (pqac-00000008) |
| Synaptic function | L-VDCC | S783 | Regulates Ca2+ influx and neurotransmitter release probability | (pqac-00000008) |
| Neuronal migration / cytoskeleton | Dcx | S710 | Regulates neuronal migration | (pqac-00000005, pqac-00000008) |
| Neuronal migration / cytoskeleton | NUDEL | S198, T219, S231 | Regulates neurite morphology and neurite outgrowth; involved in neuronal migration | (pqac-00000005, pqac-00000008) |
| Neuronal migration / cytoskeleton | FAK | S732 | Regulates microtubule organization and neuronal migration; in cancer promotes actin remodeling/EMT | (pqac-00000005, pqac-00000003) |
| Neuronal migration / cytoskeleton | RapGEF2 | S1124 | Activates Rap1 to modulate neuronal migration | (pqac-00000005) |
| Neuronal migration / cytoskeleton | Talin | S425 | Prevents Smurf1-mediated degradation of talin head domain, stabilizing lamellipodia and promoting migration | (pqac-00000003) |
| Neuronal migration / cytoskeleton | Synapsin III | S404 | Required for semaphorin-3A-elicited neuronal migration | (pqac-00000005) |
| Neuronal migration / cytoskeleton | PAK1 | T212 | Regulates neuronal migration and neurite outgrowth | (pqac-00000005, pqac-00000008) |
| Neuronal migration / cytoskeleton | Map1b | Not specified in cited context | Promotes neurite outgrowth and axonal development | (pqac-00000005) |
| Neuronal migration / cytoskeleton | Axin | T485 | Promotes axon formation; links CDK5 to Wnt pathway scaffolding | (pqac-00000005, pqac-00000008) |
| Neuronal migration / cytoskeleton | p27 | S10, S297 | Regulates nuclear elongation in migrating neurons | (pqac-00000005) |
| Mitochondrial / oxidative stress | Drp1 | S616 | Promotes mitochondrial fission; linked to neurodegeneration and cancer cell survival/death programs | (pqac-00000004, pqac-00000008, pqac-00000003) |
| Mitochondrial / oxidative stress | Parkin | S131 | Reduces Parkin E3 ubiquitin ligase activity, impairing mitochondrial quality control | (pqac-00000004, pqac-00000008) |
| Mitochondrial / oxidative stress | Prx1 | T90 | Reduces peroxidase activity, increasing oxidative stress | (pqac-00000008) |
| Mitochondrial / oxidative stress | Prx2 | T89 | Reduces peroxidase activity, increasing ROS and dopaminergic neuron loss | (pqac-00000004, pqac-00000008) |
| Tau pathology | Tau | T181, S202, T205, T217, S235, S396, S404 | Reduces microtubule binding; contributes to tau hyperphosphorylation, synaptic damage, and neurodegeneration | (pqac-00000008, pqac-00000011) |
| mTOR pathway | PRMT1 | S307 | Promotes PRMT1 translocation from nucleus to cytoplasm/lysosome, enabling WDR24 methylation and mTORC1 activation | (pqac-00000010) |
| Circadian clock | CLOCK | T451, T461 | Promotes CLOCK nuclear translocation and enhances circadian transcriptional activity | (pqac-00000008) |
| Circadian clock | PER2 | S394 | Stabilizes PER2 and promotes nuclear translocation | (pqac-00000008) |
| Other / neurodegeneration | APP | T668 | Regulates APP localization | (pqac-00000008) |
| Other / DNA damage response | ATM | S794 | Regulates DNA damage response signaling | (pqac-00000008) |
| Other / disease signaling | SIRT2 | S331, S335 | Promotes nuclear translocation of SIRT2 and dopaminergic neuronal death in Parkinson’s disease models | (pqac-00000014) |
| Other / cancer signaling | PPARγ | S273 | Releases/stabilizes ESRP1, promoting CD44 isoform switching, stemness, and metastasis in breast cancer | (pqac-00000003) |
| Other / cancer signaling | ADD1 | T724 | Reduces F-actin binding, promoting actin remodeling, migration, and invasion | (pqac-00000003) |


*Table: This table summarizes major CDK5 substrates across synaptic, cytoskeletal, mitochondrial, circadian, mTOR, and disease-related pathways, with phosphorylation sites and functional consequences. It is useful for quickly mapping CDK5’s direct molecular outputs to specific cellular processes.*