Programmed cell death 5 (PDCD5), a human apoptosis-related protein, is thought to play an early and universal role in apoptosis. PDCD5 is widely expressed and is upregulated in cells undergoing apoptosis, where it translocates rapidly from the cytoplasm to the nucleus. PDCD5 has a compact core structure of low flexibility with two mobile alpha-helices at N-terminal and a flexible unstructured C-terminal region. The charged residues are crucial for the ability of apoptosis-promoting and cell translocation of the protein. PDCD5 can facilitate apoptosis and enhance TAJ/TROY-induced paraptosis-like cell death. PDCD5 may play a dual role in the Tip60 pathway. It interacts with Tip60 and functions as a Tip60 co-activator to promote apoptosis. The nucleotide polymorphisms in the 5′-upstream region of?PDCD5 affect promoter activity and the susceptibility of a Chinese population to develop chronic myelogenous leukemia and may represent a novel tumor suppressor gene influencing lung cancer.