Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.

Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century with advancements in microscopy and histology.

While apoptosis, autophagy, and necrosis are the most commonly known types of death, some other types are necroptosis, pyroptosis, ferroptosis,entosis, and paraptosis. These types differ in their pathways toward cell death.

Necroptosis is a combination of apoptosis and necrosis. It begins when a ligand binds to death receptors, activating the receptor-interacting protein kinases-1 (RIPK-1) instead of caspase-8, generally activated during apoptosis. Further, many intermediate proteins are activated, causing cell swelling and lysis. Pyroptosis is a caspase-mediated cell death that involves caspase-1 or caspase-11, required for the maturation of inflammatory cytokines.

In ferroptosis, iron-dependent lipid peroxidation occurs, accumulating reactive oxygen species that eventually induce cell death. Prominent morphological features of ferroptosis include shrinkage of mitochondria and decreased cristae. During entosis, a cell gets internalized into the neighboring cell with the help of Rho GTPase and is then degraded by the lysosomal enzymes.

Paraptosis is activated when the insulin-like growth factor 1 receptor is overexpressed, triggering events leading to cell death. Paraptosis mainly occurs in neurons, and the paraptotic pathway is also being explored in apoptosis-resistant cancer cells. Anoikis is a programmed apoptotic cell death occurring in cells that get detached from the extracellular matrix. These cells follow the extrinsic or intrinsic pathways of apoptosis.