PQ loop repeat-containing protein 2 (PQLC2)

PQ loop repeat-containing protein 2 (PQLC2), also known as SLC66A1, is a specialized lysosomal membrane transporter responsible for the export of basic amino acids—specifically L-arginine, L-lysine, and L-histidine—from the lysosomal lumen into the cytosol [1, 2]. It plays a pivotal role in maintaining cellular amino acid homeostasis and nutrient recycling following the degradation of proteins within the lysosome [2]. Beyond its basic physiological role, PQLC2 is a critical component of the therapeutic mechanism for cystinosis; it provides an alternative exit route for cystine when converted by the drug cysteamine into a lysine-mimetic mixed disulfide [3]. In oncology, PQLC2 is increasingly recognized as a potential target because cancer cells often rely on lysosomal nutrient scavenging and PQLC2-mediated arginine export to sustain growth and activate the mTORC1 pathway under nutrient-deprived conditions [2, 3]. Consequently, modulating PQLC2 activity offers a strategic pathway for treating metabolic disorders and inhibiting tumor progression by disrupting essential nutrient signaling [1]. Sources: [1] UniProt Consortium. UniProtKB - Q96LJ7 (PQLC2_HUMAN). [2] Liu, B., et al. (2012). LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis. Science. [3] Jézégou, A., et al. (2012). Heptahelical protein PQLC2 is a lysosomal arginine exporter underlying the action of cysteamine in cystinosis. Proceedings of the National Academy of Sciences (PNAS).

Other names

SLC66A1Solute carrier family 66 member 1Lysosomal amino acid transporter 1 homologLAAT1

PQLC2 acts as a pH-dependent exporter of basic amino acids (arginine, lysine, and histidine) from the lysosomal lumen to the cytosol. In the treatment of cystinosis, it facilitates the export of the cysteamine-cysteine mixed disulfide, which structurally mimics lysine, thereby bypassing the defective cystinosin transporter.