From Gene to Clinic: The Role of APOL1 in Focal Segmental Glomerulosclerosis

Apolipoprotein L1 (<i>APOL1</i>) genetic variations, notably the G1 and G2 alleles, have important roles in the pathophysiology of focal segmental glomerulosclerosis (FSGS) and other kidney problems, especially in people of African descent. This review summarizes current understanding ab...

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Main Authors: Charlotte Delrue, Marijn M. Speeckaert
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Sclerosis
Subjects:
Online Access:https://www.mdpi.com/2813-3064/3/1/6
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author Charlotte Delrue
Marijn M. Speeckaert
author_facet Charlotte Delrue
Marijn M. Speeckaert
author_sort Charlotte Delrue
collection DOAJ
description Apolipoprotein L1 (<i>APOL1</i>) genetic variations, notably the G1 and G2 alleles, have important roles in the pathophysiology of focal segmental glomerulosclerosis (FSGS) and other kidney problems, especially in people of African descent. This review summarizes current understanding about the genetic, molecular, and clinical features of APOL1-associated FSGS and investigates new therapeutic options. It reveals how <i>APOL1</i> mutations generate kidney injury through mechanisms such as podocyte dysfunction, mitochondrial impairment, and dysregulated inflammatory networks. Recent treatment developments, such as small-molecule inhibitors like inaxaplin, antisense oligonucleotides, and novel interventions targeting lipid metabolism and inflammatory pathways, are being assessed for their capacity to address the specific issues presented by APOL1-associated nephropathy. We also address gaps in knowledge, such as the function of environmental triggers and the systemic consequences of <i>APOL1</i> mutations, emphasizing the significance of targeted research.
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series Sclerosis
spelling doaj-art-933cfc00e2294ffd8b6ce2da2d4117bb2025-08-20T02:31:13ZengMDPI AGSclerosis2813-30642025-02-0131610.3390/sclerosis3010006From Gene to Clinic: The Role of APOL1 in Focal Segmental GlomerulosclerosisCharlotte Delrue0Marijn M. Speeckaert1Department of Nephrology, Ghent University Hospital, 9000 Ghent, BelgiumDepartment of Nephrology, Ghent University Hospital, 9000 Ghent, BelgiumApolipoprotein L1 (<i>APOL1</i>) genetic variations, notably the G1 and G2 alleles, have important roles in the pathophysiology of focal segmental glomerulosclerosis (FSGS) and other kidney problems, especially in people of African descent. This review summarizes current understanding about the genetic, molecular, and clinical features of APOL1-associated FSGS and investigates new therapeutic options. It reveals how <i>APOL1</i> mutations generate kidney injury through mechanisms such as podocyte dysfunction, mitochondrial impairment, and dysregulated inflammatory networks. Recent treatment developments, such as small-molecule inhibitors like inaxaplin, antisense oligonucleotides, and novel interventions targeting lipid metabolism and inflammatory pathways, are being assessed for their capacity to address the specific issues presented by APOL1-associated nephropathy. We also address gaps in knowledge, such as the function of environmental triggers and the systemic consequences of <i>APOL1</i> mutations, emphasizing the significance of targeted research.https://www.mdpi.com/2813-3064/3/1/6Apolipoprotein L1focal segmental glomerulosclerosispodocyte injurymitochondrial dysfunction
spellingShingle Charlotte Delrue
Marijn M. Speeckaert
From Gene to Clinic: The Role of APOL1 in Focal Segmental Glomerulosclerosis
Sclerosis
Apolipoprotein L1
focal segmental glomerulosclerosis
podocyte injury
mitochondrial dysfunction
title From Gene to Clinic: The Role of APOL1 in Focal Segmental Glomerulosclerosis
title_full From Gene to Clinic: The Role of APOL1 in Focal Segmental Glomerulosclerosis
title_fullStr From Gene to Clinic: The Role of APOL1 in Focal Segmental Glomerulosclerosis
title_full_unstemmed From Gene to Clinic: The Role of APOL1 in Focal Segmental Glomerulosclerosis
title_short From Gene to Clinic: The Role of APOL1 in Focal Segmental Glomerulosclerosis
title_sort from gene to clinic the role of apol1 in focal segmental glomerulosclerosis
topic Apolipoprotein L1
focal segmental glomerulosclerosis
podocyte injury
mitochondrial dysfunction
url https://www.mdpi.com/2813-3064/3/1/6
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