Housekeeping genes are genes that are constitutively expressed in most, if not all cells. These genes encode proteins that provide the basic, essential functions that all cells need to survive (in a sense, they act as housekeepers for the cell). It is generally assumed that housekeeping genes express at the same level in all cells and tissues, but there are actually some variances, especially during cell growth and organism development. It is unknown exactly how many housekeeping genes human cells have, but most estimates are in the range from 300-500.

Many of the hundreds of housekeeping genes have been identified. The most commonly known gene, GAPDH (glyceraldehyde-3-phosphate dehydrogenase), codes for an enzyme that is vital to the glycolytic pathway. Another important housekeeping gene is albumin, which assists in transporting compounds throughout the body. Several housekeeping genes code for structural proteins that make up the cytoskeleton such as beta-actin and tubulin. Others code for 18 or 28 S rRNA, subunits of the ribosome.

Housekeeping genes are commonly used as a control in reverse transcription PCR (RT-PCR), a special form of PCR that analyzes mRNA levels in a sample instead of DNA. Since housekeeping genes are constitutively active, they produce a constant level of mRNA. They are therefore often used as a loading control to verify that identical amounts of sample were added. GAPDH is the most common control used for this method, however ideal controls vary depending on the source of the mRNA.

Lewin's Genes VI, 1997