Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1)

Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a single-pass transmembrane protein composed of leucine-rich repeat and immunoglobulin-like domains. It is primarily known as a negative regulator of multiple receptor tyrosine kinases, such as the ErbB (including EGFR), MET, RET, and PDGFR-α families. LRIG1 acts by promoting ubiquitination and lysosomal degradation of these receptors, thereby attenuating downstream proliferative and survival signaling. Functionally, LRIG1 serves as a tumor suppressor, and loss of its expression is associated with enhanced receptor signaling and increased cancer risk—particularly in epithelial tissues (e.g., intestine, skin, breast, prostate). It is also a recognized marker for quiescent stem cells in the intestine and epidermis, playing a crucial role in maintaining tissue homeostasis and restricting uncontrolled proliferation. Therapeutic targeting of pathways involving LRIG1 is under investigation, especially in the context of cancer, though broad impact on growth factor signaling raises concerns about effects on normal tissue turnover and regeneration.

Other names

LIG-1LIG1DKFZP586O1624ortholog of mouse integral membrane glycoprotein LIG-1leucine-rich repeat protein LRIG1

Promotes ubiquitination and degradation of activated growth factor receptors by facilitating their internalization and lysosomal degradation. Feedback inhibition and attenuation of aberrant tyrosine kinase signaling.