TBC1 domain-containing kinase (TBCK)

TBC1 domain-containing kinase (TBCK) is a multidomain protein classed as a pseudokinase, comprising an N-terminal serine/threonine kinase-like (pseudokinase) domain, a central TBC (Tre2-Bub2-Cdc16) domain, and a C-terminal rhodanese homology domain[1][2]. TBCK does not exhibit confirmed kinase activity due to missing essential motifs for ATP binding and catalytic function, and is therefore classified as a Class I pseudokinase[1][2]. Its best-characterized roles are as a putative Rab GTPase-activating protein and as a component of the FERRY complex, which regulates endosomal mRNA trafficking and interacts with Rab5 GTPase in neurons[2][3]. TBCK plays critical roles in neurodevelopment, with loss-of-function mutations causing TBCK syndrome, a severe infantile disorder marked by global developmental delay, muscle hypotonia, and brain abnormalities[1][2][3]. TBCK is implicated in regulating cell growth, actin organization, autophagy, mitochondrial maintenance, and mTOR signaling pathways[1][2][3]. Its links to cancer are context-dependent and remain insufficiently elucidated[1]. There are currently no known drugs or targeted therapeutics that directly engage TBCK protein.

Other names

TBC domain-containing protein kinase-like proteinTBCKLHSPC302Fy-1FERRY1MGC16169IHPRF3FERRY endosomal RAB5 effector complex subunit 1