Leucine-rich repeat-containing protein 38 (LRRC38)

Leucine-rich repeat-containing protein 38 (LRRC38) is a membrane protein that acts as an **auxiliary gamma subunit (γ4)** for the large-conductance, voltage- and calcium-activated potassium (BK) channel. LRRC38 is part of the leucine-rich repeat (LRR) protein superfamily and forms a group of BK channel auxiliary proteins termed the gamma subunits, which also includes LRRC26 (γ1), LRRC52 (γ2), and LRRC55 (γ3)[1][2][3][4]. Unlike the classic β subunits, these gamma subunits are structurally distinct, containing an N-terminal signal peptide, an extracellular LRR domain, a single transmembrane segment, and a short intracellular C-terminal tail[3]. LRRC38 is able to co-assemble with BK channel alpha subunits and modulate their activation by shifting the voltage dependence toward more negative potentials, albeit to a smaller extent (about −20 mV in absence of calcium) than other gamma subunits[1][2][3][4]. LRRC38 is mainly expressed in secretory glands and plays a role in tissue-specific regulation of BK channel gating properties, likely contributing to the functional diversity of BK channels in different cell types[2]. Direct drug interactions, disease roles, and use as a biomarker have not been established for LRRC38 as of the current literature[2][4].

Other names

BK channel auxiliary gamma subunit LRRC38BK channel auxiliary γ4 subunitγ4 (BK channel gamma 4 subunit)leucine-rich repeat-containing protein 38

LRRC38 itself does not have known small-molecule modulators; it modulates BK channel gating by association with the BK channel alpha subunit, affecting voltage dependence and channel kinetics[2][4].