Holins consist of about forty distinct families of proteins that exhibit common structural and functional characteristics but which frequently do not exhibit statistically significant sequence similarity between members of distinct families. They are encoded within the genomes of Gram-positive and Gram-negative bacteria as well as those of the bacteriophage of these organisms. Their primary function appears to be transport of murein hydrolases across the cytoplasmic membrane to the cell wall where these enzymes hydrolyze the cell wall polymer as a prelude to cell lysis. When chromosomally encoded, these enzymes are therefore autolysins. Holins may also facilitate leakage of electrolytes and nutrients from the cell cytoplasm, thereby promoting cell death. Some may catalyze export of nucleases. There are seven holin superfamilies in TCDB (Reddy and Saier 2013; Saier and Reddy 2015). Holins have been used to export bacterial recombinant proteins (Guo et al. 2022).

Although the amino acid sequences of holins are divergent, they often exhibit (1) small sizes (60-145 amino acyl residues), (2) one, two, three or four putative transmembrane spanners (TMSs), depending on the protein, each separated by a putative β-turn linker region, (3) a hydrophilic N-terminus that is localized to the cytoplasm or periplasm, and (4) a highly polar, charge-rich C-terminal domain. The murein hydrolases lack N-terminal signal sequences, and therefore are not believed to be transported via the general secretory pathway (TC #3.A.5). Holins are undoubtedly present as homooligomeric complexes that form pores through the cytoplasmic membrane which provide a passive transport function. Whether or not they function in conjunction with other proteins is not known. If not, transport of the murein hydrolase is not likely to be driven by ATP hydrolysis or by the pmf as is true for many other protein export systems (TC subclass 3.A or TC subclass 2.A, respectively).

Holins accumulate harmlessly in the cytoplasmic membrane during phage infection cycle until suddenly, at an allele-specific time, they form lethal lesions, or 'holes'. The holes caused by S105 have an average diameter of 340 nm, and some exceeding 1 micron. Most cells exhibit only one irregular hole, randomly positioned in the membrane, irrespective of its size (Dewey et al., 2010).  Holins with anti-microbial functions have been reviewed (Donovan 2007).

The generalized transport reaction catalyzed by holins is believed to be:

Murein hydrolase (in) → Murein hydrolase (out).