E3 ubiquitin-protein ligase. Together with the phosphatase EPM2A/laforin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. In complex with EPM2A/laforin and HSP70, suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Ubiquitinates the glycogen-targeting protein phosphatase subunits PPP1R3C/PTG and PPP1R3D in a laforin-dependent manner and targets them for proteasome-dependent degradation, thus decreasing glycogen accumulation. Polyubiquitinates EPM2A/laforin and ubiquitinates AGL and targets them for proteasome-dependent degradation. Also promotes proteasome-independent protein degradation through the macroautophagy pathway. S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with AGL. Interacts (via the NHL repeats) with EPM2A/laforin (By similarity). Forms a complex with EPM2A/laforin and HSP70. Interacts with PRDM8 (By similarity). Localizes at the endoplasmic reticulum and, to a lesser extent, in the nucleus. The RING domain is essential for ubiquitin E3 ligase activity. Significant impairment of motor activity, coordination and balance; spontaneous myoclonic seizures; and decreases in episodic memory. 3- and 6-month old mice contain numerous large insoluble aggregates composed mainly of polyglucosans called Lafora bodies (LBs) in skeletal muscle, liver, heart and brain. Glycogen levels are increased 1.6-fold and 1.2-fold respectively in skeletal muscle and liver of 6-month old mice. Glycogen phosphate levels are increased 1.5-fold in skeletal muscle and liver of 6-month old mice. In brain extracts from 1-, 3- and 12-month old mice, total amounts of Epm2b/laforin protein (but not mRNA) are increased. In brain and embryonic fibroblast cells, levels of the autophagy marker Map1lc3b/LC3-II are reduced. In the brain, levels of the autophagy dysfunction marker Sqstm1/p62 are increased.