Pleckstrin homology-like domain, family A, member 1 (PHLDA1), one of the three members of PHLDA (1–3) family, has been reported to be expressed in mammalian cells and tissues and play diverse roles in various biological processes such as apoptosis, pyroptosis, and differentiation. Nevertheless, new roles and mechanisms of PHLDA1 action have come to light, with some needing further clarification. The major aim of the publication is to review proapoptotic or antiapoptotic roles of PHLDA1 in cancer, including ample evidence on PHLDA1 role as a tumor suppressor gene or oncogene and its influence on tumor progression. The role of PHLDA1 as a prognostic marker of cancer emerges, as well as its role in drug response and resistance. PHLDA1 involvement in autophagy, endoplasmic reticulum stress, pyroptosis, or differentiation is also scrutinized. It is also important to note that the association of PHLDA1 with miRNA regulation is described. Additionally, the emerging functions of PHLDA1 are indicated, specifically in inflammation and ischemia/reperfusion injury.