The human genome has 5 genes for sortilin and sortilin-related proteins; SORT1, SOL1, and SORCS1-3. All of the proteins contain a VPS10 domain, and are involved in traffiking nascent proteins from the Golgi to other intracellular organelles (endosomes, lysosomes). SORT1 and SOL1 are of therapeutic interest as they participate in inducing neurodegenerative processes [1,3,5]. Antagonism of sortilin function provides neuroprotective effects [4,6-7].

1. Bøgh N, Sørensen CB, Alstrup AKO, Hansen ESS, Andersen OM, Laustsen C. (2024) Mice and minipigs with compromised expression of the Alzheimer's disease gene SORL1 show cerebral metabolic disturbances on hyperpolarized [1-¹³C]pyruvate and sodium MRI. Brain Commun, 6 (2): fcae114. [PMID:38650831]

2. Ek M, Nilvebrant J, Nygren PÅ, Ståhl S, Lindberg H, Löfblom J. (2024) An anti-sortilin affibody-peptide fusion inhibits sortilin-mediated progranulin degradation. Front Immunol, 15: 1437886. [PMID:39185427]

3. Grochowska MM, Carreras Mascaro A, Boumeester V, Natale D, Breedveld GJ, Geut H, van Cappellen WA, Boon AJW, Kievit AJA, Sammler E et al.. (2021) LRP10 interacts with SORL1 in the intracellular vesicle trafficking pathway in non-neuronal brain cells and localises to Lewy bodies in Parkinson's disease and dementia with Lewy bodies. Acta Neuropathol, 142 (1): 117-137. [PMID:33913039]

4. Jakobsen TS, Østergaard JA, Kjolby M, Birch EL, Bek T, Nykjaer A, Corydon TJ, Askou AL. (2023) Sortilin Inhibition Protects Neurons From Degeneration in the Diabetic Retina. Invest Ophthalmol Vis Sci, 64 (7): 8. [PMID:37272764]

5. Jiang J, Yang C, Ai JQ, Zhang QL, Cai XL, Tu T, Wan L, Wang XS, Wang H, Pan A et al.. (2022) Intraneuronal sortilin aggregation relative to granulovacuolar degeneration, tau pathogenesis and sorfra plaque formation in human hippocampal formation. Front Aging Neurosci, 14: 926904. [PMID:35978952]

6. Kashyap SN, Fox SN, Wilson KI, Murchison CF, Ambaw YA, Walther TC, Farese RV, Arrant AE, Roberson ED. (2024) Carboxy-terminal blockade of sortilin binding enhances progranulin gene therapy, a potential treatment for frontotemporal dementia. bioRxiv,. [PMID:39345608]

7. Kurnellas M, Mitra A, Schwabe T, Paul R, Arrant AE, Roberson ED, Ward M, Yeh F, Long H, Rosenthal A. (2023) Latozinemab, a novel progranulin-elevating therapy for frontotemporal dementia. J Transl Med, 21 (1): 387. [PMID:37322482]