This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of praliciguat in adults with biopsy-confirmed focal segmental glomerulosclerosis (FSGS). Participants will be randomized 1:1 to receive praliciguat or placebo for initial 24 week treatment period. Following this double-blind period, all participants will receive praliciguat in an open-label extension for an additional 24 weeks.

Inclusion Criteria:

1. UPCR ≥1 (g/g) during screening.
2. On maximally tolerated ACEi or ARB per principal investigator discretion within 1 month of informed consent.
3. Estimated glomerular filtration rate ≥25 milliliters per minute per 1.73 square meters by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
4. Kidney biopsy within 3 years of screening consistent with FSGS or documentation of a genetic mutation in a podocyte protein associated with FSGS.

Exclusion Criteria:

1. Collapsing FSGS in the kidney biopsy report.
2. Sickle cell disease.
3. HbA1c >8% or non-fasting blood glucose >180 milligram/decilitre.
4. Uncontrolled hypertension (≥160/100 millimeters of mercury)