The PIK3CD gene spans a genomic region of 24 coding exons and over 77.17 kb.

The dominant transcript contains two upstream untranslated exons, -2a and -1, as well as an additional first untranslated exon (-2b) identified in the human PIK3CD gene (Kok et al., 2009).

The PI3K enzymes are a family of activation dependent lipid kinases, which have been divided into three classes (Vanhaesebroeck et al., 1999a). PIK3CD encodes p110delta which belongs to the class I PI3Ks alongside p110alpha, p110beta and p110gamma.

The PI3K enzymes are heterodimeric molecules which consist of a catalytic p110 subunit, and a constitutively bound p85 regulatory unit of which there are five isoforms encoded by three genes (PIK3R1, PIK3R2 and PIK3R3) (Vanhaesebroeck and Waterfield, 1999; Geering et al., 2007).
The regulatory subunit has a dual function of recruiting the p110 catalytic subunit to an activated upstream tyrosine kinase receptor, and inhibiting catalytic activity in the absence of this stimulatory interaction (Yu et al., 1998). Unlike p110alpha, p110delta does not phoshorylate its associated p85 regulatory subunit and instead auto-phosphorylates (Vanhaesebroeck et al., 1997; Vanhaesebroeck et al., 1999a).

p110delta has a restricted expression pattern; it is highly expressed in leukocytes (Seki et al., 1997; Vanhaesebroeck et al., 1997) and to a lesser extent expressed in neurons (Eickholt et al., 2007). In addition p110delta expression has also been observed in a number of cancerous tissues including breast cancer and melanoma cells (Sawyer et al., 2003).

A transcription factor binding cluster located immediately upstream of the untranslated exon -2a in the human gene, has been identified and found to have enhanced promotor activity in leukocytes. This promoter region may therefore facilitate the enhanced expression of p110delta in leukocytes (Kok et al., 2009).

p110 delta localises to the cytosol and is recruited to the periplasmic region upon stimulation of upstream activators.

Cell signalling and lipid kinase activity. PI3K signalling has been found to play a crucial role in the regulation of numerous cellular processes including proliferation, metabolism (Foukas et al., 2006; Engelman et al., 2006), and migration (Papakonstanti et al., 2007).
Active p110delta initiates signalling cascades by phosphorylating phosphoinositide (PI) lipids such as PIP2 producing pools of PIP3 in the periplasmic region (Vanhaesebroeck et al., 1997). A wide range of effector proteins recognise and interact with the PI species produced, and the resulting alteration in location and activities of these effectors initiates a number of signalling cascades. The classical effector of PI3K signalling is the serine/threonin kinase AKT (aka protein kinase B), which contains a pleckstrin homology (PH) domain that interacts with PIP3 (Franke et al., 1997). The affinity of Akt for PIP3 facilitates activation of Akts protein kinase activity, resulting in activity-modifying phosphorylation of a range of downstream Akt targets.

Roles of p110delta in immune function. The role of p110delta in vivo has been studied in a p110delta null mouse (Clayton et al., 2002; Jou et al., 2002) and in a p110delta kinase-dead mouse known as p110delta^D910A/D910A (Okkenhaug et al., 2002). Phenotypic analysis of the p110delta^D910A/D910A mouse revealed an important role for p110delta in immunity; the mice have notable defects in their T and B cell responses, as well as several other immunological abnormalities (Okkenhaug et al., 2002). In vitro and ex vivo studies suggest that p110delta is the predominant PI3K class IA isoform regulating the phenotype and responses of many leukocyte cell types (Vanhaesebroeck et al., 1999b; Puri et al., 2004; Papakonstanti et al., 2008). In mast cells derived from the p110delta kinase-dead mice, ninety percent of the total PI3K lipid kinase activity was dependent on p110delta (Ali et al., 2004). p110delta has been found to be a key player in the induction of amongst other things, proliferation, chemotaxis, and cytokine/chemokine release in response to both physiological stimuli and pathological stimuli, in many leukocytes (Okkenhaug and Vanhaesebroeck, 2003; Dos Santos et al., 2007; Papakonstanti et al., 2008; Dil et al., 2009; Low et al., 2010).

p110delta is most homologous to p110beta (Clayton et al., 2001).

No prevalent p110delta mutations have been observed in primary samples or cell lines.