PNAS4 is a highly conserved protein that shares high homology from plants to animals. It was initially identified as a putative apoptosis-related protein in the human acute promyelocytic leukemia cell line NB4. PNAS4 is activated during the early response to DNA damage and can inhibit proliferation via apoptosis when overexpressed in some tumor cells such as U2OS, SKOV3, and A549. PNAS4 inhibits tumor cell proliferation through the following mechanisms: (i) overexpression of PNAS4 causes S phase arrest by regulating the expression of cell cycle-related proteins and (ii) PNAS4 induces apoptosis through the mitochondrial apoptosis pathway. Recent evidence has shown that PNAS4 may be involved in the genesis of some cancers and could be a potential candidate for lung cancer therapy alone or in combination with gemcitabine. At least two isoforms of PNAS4 are known to exist.