Fibronectin leucine-rich transmembrane protein 2 (FLRT2)

Fibronectin leucine-rich transmembrane protein 2 (FLRT2) is a single-pass type I transmembrane protein that is part of the FLRT family. It contains an extracellular region with an N-terminal leucine-rich repeat domain and a type 3 fibronectin domain, a transmembrane region, and a short cytoplasmic tail. FLRT2 is primarily recognized for its roles in cell adhesion, cell migration, and axon guidance. It participates in both homophilic adhesion (FLRT2-FLRT2) and heterophilic interactions, especially with members of the UNC5 receptor family (notably UNC5B, UNC5D), and other proteins such as FGFR2 and LPHN2. Through these interactions, FLRT2 regulates signaling cascades essential for neural and vascular development, and has a recently described key function in promoting the differentiation of monocytes into macrophages by activating the Akt/mTOR pathway. FLRT2 is also implicated in osteoclast maturation and various human cancers, with context-dependent roles that can either suppress or promote tumor cell migration and adhesion. Aberrant epigenetic regulation of FLRT2 (e.g., promoter hypermethylation) has been linked with prostate, breast, and colorectal cancer. FLRT2 is broadly expressed in brain, heart, skeletal muscle, and certain immune cells, and its functions suggest potential as a disease biomarker and therapeutic target in immune, neurodevelopmental, and cancer contexts

Other names

Leucine-rich repeat transmembrane protein FLRT2KIAA0405UNQ232/PRO265Fibronectin-like domain-containing leucine-rich transmembrane protein 2FLRT2

Modulation of FLRT2 interacts with UNC5B to activate Akt/mTOR pathway (for differentiation); Epigenetic regulation (e.g., methylation patterns in cancer); Potential regulation via receptor activator of nuclear factor-κB ligand (RANKL) signaling in osteoclasts