JKAMP (JNK1/MAPK8 associated membrane protein) is an endoplasmic reticulum (ER)-resident transmembrane protein that regulates protein homeostasis and MAPK8 signaling. Primary function: JKAMP facilitates degradation of misfolded ER proteins by recruiting proteasome and ER-associated degradation (ERAD) system components 1. The protein serves as a critical hub in ER quality control, where its ubiquitination by RNF5 regulates its association with proteasomal components, thereby modulating the efficiency of ERAD and GPCR trafficking 23. In disease contexts, bi-allelic JKAMP loss-of-function variants cause neurodevelopmental syndrome characterized by intellectual disability, seizures, hypotonia, and microcephaly through dysregulation of GPR37 trafficking and impaired ER quality control 4. In cancer, JKAMP is upregulated through the TTC7B-AKT axis, promoting head and neck cancer progression via enhanced cell migration and invasion 5. JKAMP emerges as an endoplasmic reticulum stress biomarker, with diagnostic potential in type 1 diabetic cardiomyopathy (ROC-AUC: 0.9349) 6. Additionally, reduced serum JKAMP levels correlate with anxiety and cognitive impairment in acute ischemic stroke patients 7. These findings establish JKAMP as a multifunctional regulator of protein quality control with significant implications for neurodevelopmental, malignant, and cardiovascular pathologies.