Abstract <p>In last decades, numerous intracellular mechanisms for neutralisation of devastating consequences of oxidative stress, which is a trigger for the development of many human pathologies, were described. Despite the active research in the field, there are a number of genes, the ability of protein products of which to protect the cells from the consequences of oxidative stress has been known for a long time, but the molecular mechanisms of their work remain poorly studied. First of all, such genes include <i>TLDc</i> gene family members. In mammal genomes, the <i>TLDc</i> family comprises five members—<i>Oxr1</i>, <i>Ncoa7</i>, <i>Tbc1d24</i>, <i>mEAK7</i> and <i>TLDc2</i> gene, and some of the genes encode multiple isoforms. The family members (united by the presence of a conservative TLDс domain) are expressed in a wide range of organs and tissues at different stages of ontogenesis in many organisms (from protozoans to humans), and mutations in the <i>TLDc</i> domain are associated with the pathological phenotype development. Molecular function of TLDc family proteins is unknown; however, it has been shown that they can protect cells from oxidative stress in vitro and in vivo, as well as regulate the functions of lysosomes and other membrane organelles in the cell via interaction with vesicular ATPase. Overexpression of some of <i>TLDc</i> family genes in animal models of various pathologies had a protective effect. This review covers known molecular functions of TLDc family proteins, their evolutionary conservation, as well as their role in different human and animal pathological conditions.</p>