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Sitosterolemia is a rare autosomal recessive disorder characterized by impaired excretion of plant sterols, leading to their accumulation in tissues and organs. We identified a hitherto unreported homozygous variant, in ATP-binding cassette sub-family G member 5 (ABCG5) (NM_022436.3) c.274A>G p.(Lys92Glu), segregating in two affected sibs (Sit1C and Sit1F) of a consanguineous Pakistani family, during genetic workup for hereditary hemolytic anemia. Both patients had anemia, history of gum bleed and easy bruising. Peripheral film revealed stomatocytes and macrothrombocytopenia. Plasma sitosterol level was found to be significantly high (27.7 mg/dL and 25.1 mg/dL for Sit1C and F respectively), confirming diagnosis of sitosterolemia in both patients. Treatment with Ezetimibe, a sterol absorption inhibitor, resulted in significant decrease in sitosterol as well as LDL-cholesterol, in these patients. This study confirms the potential of panel sequencing as a diagnostic tool for sitosterolemia. Definitive diagnosis has significant clinical implications for genetic counseling and management strategies, such as dietary modifications and successful management with Ezetimibe., Competing Interests: Declaration of competing interest The authors have no conflicts of interest related to the present study to disclose., (Copyright © 2024. Published by Elsevier Inc.)