This is a family of 5 evolutionarily related proteins. Their structural similarities suggest that they are transporters. Biochemical evidence supports transporter activity for SLC66A1 (LAAT1) and SLC66A4 (CTNS; Cystinosin), primarily exporting amino acids from the lysosome to the cytoplasm. The functions of the 3 remaining members of the family are undetermined.

* Key recommended reading is highlighted with an asterisk

* Jézégou A, Llinares E, Anne C, Kieffer-Jaquinod S, O'Regan S, Aupetit J, Chabli A, Sagné C, Debacker C, Chadefaux-Vekemans B et al.. (2012) Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy. Proc Natl Acad Sci U S A, 109 (50): E3434-43. [PMID:23169667]

* Kalatzis V, Cherqui S, Antignac C, Gasnier B. (2001) Cystinosin, the protein defective in cystinosis, is a H(+)-driven lysosomal cystine transporter. EMBO J, 20 (21): 5940-9. [PMID:11689434]

* Kandasamy P, Gyimesi G, Kanai Y, Hediger MA. (2018) Amino acid transporters revisited: New views in health and disease. Trends Biochem Sci, 43 (10): 752-789. [PMID:30177408]

* Liu B, Du H, Rutkowski R, Gartner A, Wang X. (2012) LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis. Science, 337 (6092): 351-4. [PMID:22822152]

* Ruivo R, Bellenchi GC, Chen X, Zifarelli G, Sagné C, Debacker C, Pusch M, Supplisson S, Gasnier B. (2012) Mechanism of proton/substrate coupling in the heptahelical lysosomal transporter cystinosin. Proc Natl Acad Sci U S A, 109 (5): E210-7. [PMID:22232659]

1. Amick J, Tharkeshwar AK, Talaia G, Ferguson SM. (2020) PQLC2 recruits the C9orf72 complex to lysosomes in response to cationic amino acid starvation. J Cell Biol, 219 (1). [PMID:31851326]

2. Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E. (2016) Cystinosis: a review. Orphanet J Rare Dis, 11: 47. [PMID:27102039]

3. Jézégou A, Llinares E, Anne C, Kieffer-Jaquinod S, O'Regan S, Aupetit J, Chabli A, Sagné C, Debacker C, Chadefaux-Vekemans B et al.. (2012) Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy. Proc Natl Acad Sci U S A, 109 (50): E3434-43. [PMID:23169667]

4. Kalatzis V, Cherqui S, Antignac C, Gasnier B. (2001) Cystinosin, the protein defective in cystinosis, is a H(+)-driven lysosomal cystine transporter. EMBO J, 20 (21): 5940-9. [PMID:11689434]

5. Kranz C, Denecke J, Lehrman MA, Ray S, Kienz P, Kreissel G, Sagi D, Peter-Katalinic J, Freeze HH, Schmid T et al.. (2001) A mutation in the human MPDU1 gene causes congenital disorder of glycosylation type If (CDG-If). J Clin Invest, 108 (11): 1613-9. [PMID:11733556]

6. Leray X, Conti R, Li Y, Debacker C, Castelli F, Fenaille F, Zdebik AA, Pusch M, Gasnier B. (2021) Arginine-selective modulation of the lysosomal transporter PQLC2 through a gate-tuning mechanism. Proc Natl Acad Sci U S A, 118 (32). [PMID:34344826]

7. Liu B, Du H, Rutkowski R, Gartner A, Wang X. (2012) LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis. Science, 337 (6092): 351-4. [PMID:22822152]

8. Ruivo R, Bellenchi GC, Chen X, Zifarelli G, Sagné C, Debacker C, Pusch M, Supplisson S, Gasnier B. (2012) Mechanism of proton/substrate coupling in the heptahelical lysosomal transporter cystinosin. Proc Natl Acad Sci U S A, 109 (5): E210-7. [PMID:22232659]

9. Schenk B, Imbach T, Frank CG, Grubenmann CE, Raymond GV, Hurvitz H, Korn-Lubetzki I, Revel-Vik S, Raas-Rotschild A, Luder AS et al.. (2001) MPDU1 mutations underlie a novel human congenital disorder of glycosylation, designated type If. J Clin Invest, 108 (11): 1687-95. [PMID:11733564]

10. Talaia G, Amick J, Ferguson SM. (2021) Receptor-like role for PQLC2 amino acid transporter in the lysosomal sensing of cationic amino acids. Proc Natl Acad Sci U S A, 118 (8). [PMID:33597295]

11. Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, Callen DF, Gribouval O, Broyer M, Bates GP et al.. (1998) A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat Genet, 18 (4): 319-24. [PMID:9537412]

Gergely Gyimesi Department for BioMedical Research Universität Bern Murtenstrasse 35 CH-3008 Bern Switzerland Matthias A. Hediger Department for BioMedical Research Universität Bern Murtenstrasse 35 CH-3008 Bern Switzerland