Nuclear lamins, a crucial type of intermediate filament protein, primarily form the inner nuclear membrane and are essential for maintaining nuclear integrity throughout various cell cycle stages. However, recent research has uncovered their broader functions as key scaffolds in nuclear sub-compartmentalization, 3D genome organization, and gene regulation. These functions are dynamically regulated by several post-translational modifications (PTMs), including phosphorylation, acetylation, SUMOylation, methylation, ubiquitination, farnesylation, and O-GlcNAcylation. Lamin PTMs influence chromatin stability, nuclear organization, stress responses, cellular differentiation, metabolism, and ageing. The pathological implications of lamin dysfunction are profound. Altered PTM patterns have been associated with multiple disorders, including laminopathies, metabolic syndromes, premature ageing diseases like Hutchinson–Gilford progeria, and even cancer. This chapter discusses how dysregulated lamin PTMs lead to nuclear instability and chromatin disorganization and contribute to disease progression. Understanding how PTMs affect lamin function opens avenues for therapeutic strategies targeting lamin-related disorders. This research is critical for developing innovative treatments aimed at restoring nuclear integrity and normal cellular function, ultimately improving disease outcomes.