LRRK1
LRRK1 is a large multidomain protein combining ankyrin repeats, a leucine-rich repeat region, a RAS-like GTPase (ROC) domain, a COR element and a kinase domain of the TKL group. Compared with its paralog LRRK2, LRRK1 is less studied but plays a critical role in bone homeostasis: homozygous loss-of-function mutations cause osteosclerotic metaphyseal dysplasia, a disorder of excessive bone density, and mouse models show that LRRK1 regulates osteoclast ruffled-border formation and bone resorption. LRRK1 has also been reported in EGFR trafficking and cell growth signaling. Recombinant LRRK1 kinase-domain constructs support enzymatic characterization and mechanistic studies of skeletal disease.
