Familial partial lipodystrophy (FPLD) is a rare inherited disorder characterized by selective loss of subcutaneous fat and severe metabolic complications. Eight subtypes of FPLD have been described to date, most of which are caused by variants in genes involved in adipocyte differentiation and lipid metabolism. The most common form, FPLD type 2, is caused by heterozygous variants in the LMNA gene, whereas much rarer forms, such as FPLD type 6, are associated with biallelic variants in LIPE. Here, we describe five patients carrying novel or ultrarare pathogenic variants in LMNA (p.Lys117Arg, p.Asn195Tyr, p.Ser239Arg, p.Lys515Glu) and LIPE (homozygous p.Val1068GlyfsTer102), thereby expanding the known genetic and phenotypic spectrum of FPLD. All individuals exhibited abnormal fat distribution and metabolic disturbances, with considerable interindividual variability in the extent and pattern of adipose tissue loss and accumulation. LMNA-related cases showed cardiac involvement, whereas the LIPE-related case presented peculiar patterns of fat redistribution and specific clinical features. These findings underscore the importance of genetic testing in patients with otherwise unexplained lipodystrophy to facilitate early diagnosis, guide personalized management, enable family screening, and support long-term multidisciplinary follow-up for monitoring metabolic, cardiovascular, and systemic complications.