According to Entrez-Gene, human PLA2G4A maps to locus NC_000001.10. This gene contains 18 exons that encompass approximately 160 kb of genomic DNA. In mice, Pla2g4a maps to NC_000067.5 and contains 18 exons that span 131 kb of DNA within the mouse genome.

Human PLA2G4A mRNA (NG_024420) consists of 2940 bp, and murine Pla2g4a mRNA (NM_008869) contains 2846 bp.

No pseudogene has been identified for PLA2G4A.

cPLA2alpha is an 85 kDa protein consisting of 749 amino acids. cPLA2alpha belongs to the alpha-beta hydrolase family which is identified by a characteristic nucleophile elbow with a consensus sequence of Sm-X-Nu-Sm (Sm = small residue, X = any residue and Nu = nucleophile). The protein contains an N-terminal C2 domain (Ca²⁺-dependent, phospholipid binding) and two catalytic domains (alpha/beta hydrolase). The N-terminal region of the first catalytic domain contains the lipase consensus sequence, GXSGS. At the active site, cPLA2alpha contains a serine nucleophile (Ser228) through which the catalytic mechanism is initiated. The active site is partially covered by a solvent-accessible flexible lid which spans from Arg413 to Gln457. cPLA2alpha displays interfacial activation as it exists in both "closed lid" and "open lid" forms. Upon membrane binding, gross conformational changes in the enzyme result in the movement of the cPLA2alpha lid thus exposing a greater hydrophobic surface and the active site. This allows the fatty acyl chain of a substrate phospholipid molecule to enter the active site.

cPLA2alpha is ubiquitously expressed throughout normal tissues, but is often overexpressed in human cancers.

Prior to activation, cPLA2alpha is localized to the cytoplasm. Upon an influx of intracellular calcium (Ca²⁺), however, Ca²⁺ ions bind to the C2 domain and promote the translocation of cPLA2alpha to either the nuclear envelope, Golgi apparatus, endoplasmic reticulum, or plasma membrane. The membrane-associated localization is then stabilized through the binding of the protein to anionic phospholipids or by phosphorylation of Ser505, Ser515, or Ser727. As a result of these molecular events, the enzymatic activity of cPLA2alpha is increased.

Following activation by Ca²⁺ concentration and/or phosphorylation, cPLA2alpha hydrolyzes phospholipids at the sn-2-acyl ester bond to yield both free fatty acid as well as lysophospholipid second messengers.
Phosphatidylcholine (PC) is the most abundant phospholipid in mammalian cell membranes and is the primary target of cPLA2alpha. The cPLA2alpha-mediated cleavage of PC results in the release of arachidonic acid (AA) and lysophosphatidylcholine (LPC). AA is further metabolized to prostaglandins and leukotrienes by the cyclooxygenase and 5-lipoxygenase pathways, respectively. Thus, cPLA2alpha and AA are key contributors to the inflammatory process. Lipid second messengers such as LPC and lysophosphatidic acid (LPA) are involved in downstream signal transduction that affects cell survival, proliferation, motility, and invasiveness.

Homologs of human PLA2G4A have been identified in the following organisms : Pan troglodytes, Canis lupus familiaris, Bos taurus, Mus musculus, Rattus norvegicus, Gallus gallus, Danio rerio. In addition, at least four paralogs of cPLA2 have been identified in mammals. They include cPLA2alpha, cPLA2beta, cPLA2gamma, and cPLA2delta. All paralogs contain the N-terminal C2 domain except cPLA2gamma. Human cPLA2gamma also harbors a myristoylation site at the N-terminus and is farnesylated at the C-terminus. The main residues that are essential to cPLA2 catalytic activity (Arg200, Ser228, Asp549, Arg566) are conserved among all four paralogs of the enzyme.

In a study performed on 118 British family trios of schizophrenia patients, six single nucleotide polymorphisms (SNPs) were identified in the PTGS2/PLA2G4A locus. SNP4 was detected in the 5-flanking region of the gene and was associated with elevated susceptibility to schizophrenia.
In a separate study of inherited prostanoid biosynthesis deficiency, a patient was found to possess three mutations of the PLA2G4A gene (S111P, R485H, and K651R). As a result of these mutations, the patient suffered from recurrent ulcerations of the small intestine and repeated episodes of gastrointestinal bleeding. Thus, such findings suggest that cPLA2alpha is important for maintaining the integrity of the small intestine.

Overexpression of cPLA2alpha has been identified in a variety of cancers including Non-small cell lung cancer (NSCLC), cholangiosarcomas, esophageal cancers, and cancers of the colon and small intestine. In many cases of NSCLC, cPLA2alpha expression is often associated with the presence of oncogenic Ras mutations.