Lamin B2 (LMNB2), on the inner side of the nuclear envelope, constitutes the nuclear skeleton by connecting with other nuclear proteins. LMNB2 is involved in a wide range of nuclear functions, including DNA replication and stability, regulation of chromatin, and nuclear stiffness. Moreover, LMNB2 regulates several cellular processes, such as tissue development, cell cycle, cellular proliferation and apoptosis, chromatin localization and stability, and DNA methylation. Besides, the influence of abnormal expression and mutations of LMNB2 has been gradually discovered in cancers and laminopathies. Therefore, this review summarizes the recent advances of LMNB2-associated biological roles in physiological or pathological conditions, with a particular emphasis on cancers and laminopathies, as well as the potential mechanism of LMNB2 in related cancers.