The multifaceted roles of receptor tyrosine pseudokinases in cellular signalling

Receptor tyrosine pseudokinases comprise approximately 10% of the receptor tyrosine kinase family and lack phosphotransferase activity due to substitutions of essential catalytic residues within their kinase folds. This review critically examines the eight human receptor tyrosine pseudokinases: EphA10, EphB6, HER3, PTK7, ROR1, ROR2, RYK, and STYK1. By reconciling recent structural and functional data, we highlight the diverse non-catalytic mechanisms these pseudokinases employ in cellular communication. This comprehensive analysis provides insights into non-canonical signalling pathways and highlights potential for therapeutic opportunities in diseases associated with pseudokinase dysfunction.