LRRK1 (leucine-rich repeat kinase 1) is a serine/threonine protein kinase that regulates intracellular trafficking through phosphorylation of RAB proteins 1. Unlike its paralog LRRK2, LRRK1 specifically phosphorylates RAB7A at Ser72, with this activity being dependent on protein kinase C (PKC) activation 2. The kinase exhibits a unique autoinhibition mechanism that differs from LRRK2, being sterically autoinhibited in a dimer-dependent manner with an additional level of autoinhibition absent in LRRK2 3. LRRK1 interacts with epidermal growth factor receptor (EGFR) and translocates to endosomes upon EGF stimulation, distinguishing it from LRRK2's 14-3-3 protein interactions 4. The kinase plays a role in negative regulation of bone mass through osteoclast maturation [UniProt]. Disease-wise, LRRK1 is associated with osteosclerotic metaphyseal dysplasia and dysosteosclerosis, with mutations typically being autosomal recessive loss-of-function variants, contrasting with LRRK2's autosomal dominant gain-of-function mutations in Parkinson's disease 35. PPM1H phosphatase counteracts LRRK1 activity by dephosphorylating phospho-RAB7A 2. These distinct substrate specificities and regulatory mechanisms suggest LRRK1 and LRRK2 evolved specialized functions despite their structural similarity.