Kufs’ disease is a rare, adult-onset form of a group of neurodegenerative disorders known as neuronal ceroid lipofuscinoses (NCLs). Although some of the genetic and cellular defects underlying early-onset, inherited NCLs have been identified, the causes of Kufs’ disease are less clear. Through genetic analyses of American Staffordshire terriers that suffer from a late-onset form of NCL, Abitbol et al. uncovered a role for a lysosomal sulfatase, arylsulfatase G (ARSG), in disease pathology. The researchers found that an NCL-associated mutation near the region of ARSG encoding the enzyme’s catalytic domain caused a 75% reduction in its sulfatase activity, supporting previous findings that lysosomal defects underlie NCLs. These findings reveal a role for ARSG in regulating neuronal homeostasis and open up the possibility that sulfatase deficiency might cause or modify the pathology of NCLs in humans.

Abitbol
M
,
Thibaud
JL
,
Olby
NJ
,
Hitte
C
,
Puech
JP
,
Maurer
M
,
Pilot-Storck
F
,
Hédan
B
,
Dréano
S
,
Brahimi
S
, et al. 
(
2010
).
A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis
.
Proc. Natl. Acad. Sci. USA
Aug 2 [Epub ahead of print] [doi: ]