PSKH2 (protein serine kinase H2) is a pseudokinase located on chromosome 8.3 that evolved through species-level adaptations from the canonical kinase PSKH1 within the CAMK family. Unlike its active relative, PSKH2 is catalytically inactive in primates, lacking the invariant catalytic aspartate residue required for protein phosphotransferase activity 1. Structurally, PSKH2 contains an N-terminal myristoylation site required for stable expression and membrane-rich subcellular localization, including mitochondrial compartments 1. The protein functions through a catalysis-independent mechanism, operating as part of a mitochondrial protein network regulated by the HSP90/Cdc37 molecular chaperone system through its C-terminal tail 1. While PSKH2's precise physiological role remains unclear 2, recent evidence indicates it contributes to genetic variance in Factor V plasma levels through interactions with neutrophil biology and smoking-related loci (GRIN2A and POM121L12) 3. Additionally, PSKH2 variants have been identified as potential genetic modifiers of clinical phenotype variability in hereditary angioedema 4. These findings establish PSKH2 as a functionally important pseudokinase whose signaling operates through conformational mechanisms rather than canonical kinase catalysis.