Leucine-rich repeat and calponin homology domain-containing protein 4 (LRCH4)

Leucine-rich repeat and calponin homology domain-containing protein 4 (**LRCH4**) is a membrane-associated protein characterized by an N-terminal leucine-rich repeat (LRR) ectodomain that forms a horseshoe-like structure involved in ligand capture, a central intrinsically disordered region, and a C-terminal calponin homology (CH) domain, often accompanied by a transmembrane segment. LRCH4 plays a regulatory role in innate immune signaling and is necessary for optimal activation of Toll-like receptor 4 (TLR4) in response to bacterial lipopolysaccharide (LPS). It contributes to downstream induction of both MyD88-dependent and TRIF-dependent cytokines, as well as activation of transcription factors such as NF-κB and IRF3 after LPS exposure. LRCH4 is hypothesized to mediate organization and activity within lipid raft microdomains, possibly facilitating efficient TLR4 clustering and signaling. Additionally, LRCH4 interacts with cytoskeletal partner proteins (such as Coro1A) and may impact cell division, proliferation, and actin dynamics as part of broader cellular functions. While not itself a conventional receptor, LRCH4 acts as an accessory or scaffold protein in innate immune receptor complexes. It is widely expressed, evolutionarily conserved, and currently under study as a potential molecular target in inflammatory and infectious diseases.

Other names

LRRN4LRRN1LRNPP14183Leucine-rich repeat neuronal protein 4Leucine-rich neuronal proteinleucine-rich repeat and calponin homology (CH) domain containing 4

Not applicable; no direct drugs currently interact with LRCH4. Mechanistically, future drugs might aim to modulate innate immune signaling or TLR4 pathway if targeting LRCH4.