In the 1990s and early 2000s, new enzymes from this family were discovered that did not follow all the classical criteria of this enzyme class, and new subfamily nomenclature was developed to divide this large family into subcategories based on deviations from typical characteristics of type II enzymes.
I 1990'erne og begyndelsen af 2000'erne blev nye enzyme fra denne familie, som ikke fulgte alle de klassiske kriterier for denne enzymklasse, opdagede, og en ny nomenklatur for underfamilier blev udviklet i henhold til at inddele denne store familie i underkategorier baseret på afvigelserne fra de typiske karakteristika for type II-restriktionsenzymer.