First the story: I extend my Localized Thieves Guild Jobs with job targets in all hold capitals. Those small cities have very few shops so I need all those I can use. In Morthal for example there's only the Inn and the Thaumaturgist's Hut. For those jobs to function (the one with the ledger and the two with the strongbox) the shop needs an actor with Location Ref Type = Boss, and I don't want to change that for the entire system and affect all vanilla quests.
Unfortunately Lami, the owner or the Thaumaturgist's Hut, has her editor location at her house (Jorgen and Lamy's House). The question is how can I set her to be "Boss" for the shop if her editor location is somewhere else? Can I do that or what are the less invasive changes I could make?

I think "Boss" is just a keyword(s) that goes on an actor?? ... The Radiant System picks the nearest "Boss" tagged character to the dungeon it has chosen?

Is not a keyword, is about this: http://www.creationkit.com/Location_Ref_Type
I believe my option is to move Lami in the CK to the shop. Is that safe, without needing a new game?

Are you sure the location ref type check is not made at the cell were the ref is instead of in the cell the reference is created in the CK? that would made the ref type system a lot less useful.

I don't understand which way you think is less useful. I believe Loc Ref Type is the way to have a relation between the role of certain references within a location which is useful and no other means for it, for other purposes keywords will simply work.
I didn't followed NPC around but I definitely believe the check is made at the location where is defined seeing how those thieves guild radiant quests are made. It won't make any sense for an NPC to be the "boss" of the streets while it moves around out of it's house. You can't assign a Loc Ref Type in any other place than the window shown here: http://www.creationkit.com/Location_Ref_Type#Use which pops up from the render view or at last I didn't find any other place to assign it...if there is that would answer my OP question.
Also from here http://www.creationkit.com/Location :
Location Ref Types

Lists the http://www.creationkit.com/Location_Ref_Type associated with the location (not current place of the reference but THE location, my comment). Double-clicking on any of the loc ref types will load up the cell in the http://www.creationkit.com/Render_Window and select the reference that has that location ref type.

Boss in vanilla skyrim is a keyword. Same as LocTypeInn for example.

To fill targetaliases you may check how the bounty quest has done it and change accordingly. (for example the lcoation has keyword loctypetemple and the target is an actor + some conditions.)

There may be a also keyword, but there's definitely a Location Ref type "boss". See where "boss" is always in the examples:
http://www.creationkit.com/Location#Location_Dialog
http://www.creationkit.com/Bethesda_Tutorial_Dungeon_Wrapup#Location_Reference_Types_and_Radiant_Story

And I had enough research on those guild jobs, no need for other examples. Remember I extend an already existing system with targets, not create new quests, I believe I understand them well. The only issue is with Lami's shop as described in OP, every thing else works like a charm.

It is a keyword for EncTrollFrost in first picture.

Then create a new aliasref with haskeyword blahhold, loctypeshop or something. Make the target with female, race etc and only Lami should be filled in.

I understand what you say, there's always ways to do something like this in different ways. BUT, I extend the existing Vex, Delvin jobs with targets, the filling conditions are already there, I don't want to change everything like how the vanilla targets in major cities are picked just because of this one single shop.

Do you need to use existing NPCs? Maybe place someone or something else, visible or invisible in the place as a boss dummy?