Objective <p>To characterize the clinical features and identify genotype-phenotype correlation in patients with maturity-onset diabetes of the young type 5 (MODY5).</p> Methods <p>We conducted a retrospective observational study on seven patients with genetically confirmed HNF1B molecular defects from a single center in India. We also performed a systematic review of the literature following the guidelines of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). Genetically proven MODY5 patients were searched in the English literature published between 1997 and November 2023.</p> Results <p>Out of 435 patients with MODY5, 71.7% were diagnosed before the age of 25. A family history of diabetes was present in 73.2%, with three successive generation involvement in 36.1%. Insulin therapy was needed in 81.5%. Diabetic ketoacidosis occurred in 16.6%. Pancreatic structural abnormalities were seen in 54%, often absent tails/bodies. 47.5% showed pancreatic exocrine insufficiency, 56.3% had hyperechoic kidneys, 23.7% had ureteric abnormalities, 12% had nephrocalcinosis/nephrolithiasis, 46.7% of women had uterine abnormalities, and 37.5% of men had epididymal cysts. Hypomagnesemia and hypokalemia occurred in 56.2% and 28.6%, respectively. Patients with 17q12 deletions required more insulin, had more neuro-psychiatric issues, and had a higher prevalence of hypomagnesemia. In contrast, retinopathy was commoner in the mutation group. Renal and genital anomalies and mean eGFR were similar between deletion and HNF1B mutation groups.</p> Conclusions <p>Diagnosis of MODY5 is often challenging due to its varied presentation. This study provides a comprehensive analysis of the phenotypic characteristics of such individuals. The findings underscore the importance of considering MODY5 in young patients with diabetes mellitus, especially those with a family history, pancreatic structural abnormalities, and relevant extra-pancreatic features.</p>