Summary and conclusions from the present affinity capture approach to VLGR1 function and for VLGR1 signaling pathways. (a) TAP prey related to ciliary and retinal function were mainly found with full-length VLGR1a. VLGR1_CTF was sufficient for focal adhesion and synaptic protein binding. Both full-length and VLGR1_CTF interact with proteins involved in neuron projection formation, cellular homeostasis, transcription regulation, cell cycle regulation, and pre-mRNA splicing. VLGR1_ICD binds to PDZ domain-containing scaffold proteins. (b) COL18A1 and SLIT2 are potential extracellular ligands for VLGR1, interacting with its NTF. VLGR1 full-length was linked to HIF-1 signaling coupled to Gαi and Gαs. VLGR1_CTF is coupled to Gαi and linked to Wnt, Notch, and Ephrin signaling; VLGR1_ICD seems to be linked to MAPK signaling.