SLIT and NTRK-like protein 5 (SLITRK5)

SLIT and NTRK-like protein 5 (SLITRK5) is a single-pass transmembrane protein characterized by two extracellular leucine-rich repeat (LRR) domains and a conserved intracellular region with tyrosine residues. It is highly expressed in the central nervous system, where it plays key roles in the development of neuronal circuits, including the regulation of axon and dendritic growth, neuron differentiation, and synaptogenesis, especially of inhibitory synapses[1][4]. SLITRK5 interacts with synaptic adhesion molecules such as receptor protein tyrosine phosphatases (e.g., PTPRD) and also acts as a co-receptor for the BDNF-TrkB pathway, influencing neuronal signaling and plasticity[1]. In non-neuronal tissues, such as osteoblasts, SLITRK5 serves as a negative regulator of Hedgehog signaling by binding to Sonic Hedgehog (SHH) and interacting with the PTCH1 receptor, thus modulating bone formation[2]. Mutations or altered expression of SLITRK5 have been linked to several CNS disorders, including obsessive-compulsive disorder, ADHD, autism spectrum disorders, Parkinson's disease, and gliomas[1][4]. Although it is a notable target in CNS and bone biology research, there are currently no approved drugs that directly target SLITRK5, and its precise therapeutic potential and safety profile remain under investigation.

Other names

SLITRK5KIAA0918LRRC11bA364G4.2Leucine-rich repeat-containing protein 11slit and trk like gene 5

Potential modulation by targeting protein–protein interactions (e.g., blocking its interaction with synaptic adhesion molecules or Hedgehog pathway components) Targeting co-receptor function to enhance or inhibit related signaling pathways (e.g., Hedgehog, BDNF-TrkB)